Subtropical evergreen broad-leaved trees are usually vulnerable to freezing stress,while hexaploid wild Camellia oleifera shows strong freezing tolerance.As a valuable genetic resource of woody oil crop C.oleifera,wil...Subtropical evergreen broad-leaved trees are usually vulnerable to freezing stress,while hexaploid wild Camellia oleifera shows strong freezing tolerance.As a valuable genetic resource of woody oil crop C.oleifera,wild C.oleifera can serve as a case for studying the molecular bases of adaptive evolution to freezing stress.Here,47 wild C.oleifera from 11 natural distribution sites in China and 4 relative species of C.oleifera were selected for genome sequencing.“Min Temperature of Coldest Month”(BIO6)had the highest comprehensive contribution to wild C.oleifera distribution.The population genetic structure of wild C.oleifera could be divided into two groups:in cold winter(BIO6≤0℃)and warm winter(BIO6>0℃)areas.Wild C.oleifera in cold winter areas might have experienced stronger selection pressures and population bottlenecks with lower N_(e) than those in warm winter areas.155 singlenucleotide polymorphisms(SNPs)were significantly correlated with the key bioclimatic variables(106 SNPs significantly correlated with BIO6).Twenty key SNPs and 15 key copy number variation regions(CNVRs)were found with genotype differentiation>50%between the two groups of wild C.oleifera.Key SNPs in cis-regulatory elements might affect the expression of key genes associated with freezing tolerance,and they were also found within a CNVR suggesting interactions between them.Some key CNVRs in the exon regions were closely related to the differentially expressed genes under freezing stress.The findings suggest that rich SNPs and CNVRs in polyploid trees may contribute to the adaptive evolution to freezing stress.展开更多
Chinese hamster with Chinese characteristics is used in experiments,and it is of great value in the field of medical biology research.However,at present,there is no high-efficiency method for evaluating the genetic qu...Chinese hamster with Chinese characteristics is used in experiments,and it is of great value in the field of medical biology research.However,at present,there is no high-efficiency method for evaluating the genetic quality of Chinese hamsters.Here,we developed a novel Chinese hamster genetic quality detection system using single-nucleotide polymorphism(SNP)markers.To find SNP loci,we conducted whole genome sequencing on 24 Chinese hamsters.Then,we employed an SNP locus screening criterion that we set up previously and initially screened 214 SNP loci with wide genome distribution and high polymorphism level.Subsequently,we developed the SNP detection system using a multitarget region capture technique based on second-generation sequencing,and a 55 SNP panel for genetic evaluation of Chinese hamster populations was developed.PopGen.32.analysis results showed that the average effective allele number,Shannon index,observed heterozygosity,expected heterozygosity,average heterozygosity,polymorphism information,and other genetic parameters of Chinese hamster population A were higher than those in population B.Using scientific screening and optimization,we successfully developed a novel Chinese hamster SNP genetic detection system that can efficiently and accurately analyze the genetic quality of the Chinese hamster population.展开更多
Multiplex polymerase chain reaction （PCR） has been widely used to detect Y-chromosome micredeletions, which is one of the major causes of male infertility. Both the European Academy of Andrology （EAA） and the Euro...Multiplex polymerase chain reaction （PCR） has been widely used to detect Y-chromosome micredeletions, which is one of the major causes of male infertility. Both the European Academy of Andrology （EAA） and the European Molecular Genetics Quality Network （EMQN） have recommended the use of sY84 and sY86 markers for the detection of azoospermia factor a （AZFa） microdeletion during DNA testing for male infertility. In this study, a large-scale analysis of AZF microdeletion in a total of 630 Chinese males, including healthy semen donors （n=200）, infertile males with normal sperm count （n=226） and patients with either nonobstructive azoospermia or severe oligozoospermia （n=204）, was performed. A series of nine sequence-tagged site （STS） markers from the AZF region of the Y chromosome was used to detect microdeletions. All primers were designed based on the recommendations of the National Center for Biotechnology Information. An unusually high incidence （73/630, 11.6%） of sY84-absent but sY86-present genotypes was observed in the AZFa microdeletion screening. Sequencing the sY84-flanking region revealed a total of 73 patients with sY84-absent but sY86-present genotypes have a T-to-G transversion at the fifth base from the 5＇ end of the reverse sY84 primer. These prevalent false positives, which were not only observed in infertile men, but also observed in donors, resulted from a single-nucleotide polymorphism （SNP） named rs72609647 in the targeting sequence of the reverse sY84 primer. Our study suggests that a pre-screening of existence of rs72609647 polymorphism can prevent the frequent false positive results of AZFa microdeletions detection in the infertile Chinese males. Given the SNP rs72609647 was recently found in a deep sequencing of a Chinese individual, the current EAA and EMQN standards may need to be scrutinized among different populations to avoid the potential genetic variations in the primer binding sequences.展开更多
BACKGROUND Polygonum multiflorum is one of the leading causes of herb-induced liver injury in China.HLA-B*35:01 is reported to be a potential biomarker of Polygonum multiflorum-induced liver injury(PM-DILI).However,li...BACKGROUND Polygonum multiflorum is one of the leading causes of herb-induced liver injury in China.HLA-B*35:01 is reported to be a potential biomarker of Polygonum multiflorum-induced liver injury(PM-DILI).However,little is known about the relationship between single-nucleotide polymorphisms(SNPs) and PM-DILI.AIM To identify SNPs that indicate susceptibility to PM-DILI METHODS We conducted a systematic study enrolling 382 participants from four independent hospitals,including 73 PM-DILI patients,118 patients with other drug-induced liver injury(other-DILI) and 191 healthy controls.Whole-exome sequencing was performed for 8 PM-DILI patients and 8 healthy controls who were randomly selected from the above subjects.Nineteen SNPs that showed high frequencies in the 8 PM-DILI patients were selected as candidate SNPs and then screened in 65 PM-DILI patients,118 other-DILI patients and 183 healthy controls using the MassARRAY system.HLA-B high-resolution genotyping was performed for the 73 PM-DILI and 118 other-DILI patients.The Han-MHC database was selected as a population control for HLA-B analysis.P <6.25 x 103 after Bolferroni correction was considered significant.RESULTS The frequencies of rslll686806 in the HLA-A gene,rs1055348 in the HLA-B gene,and rs202047044 in the HLA-DRB1 gene were significantly higher in the PM-DILI group than in the control group [27.2% vs 11.6%,P=1.72×105,odds ratio(OR)=3.96,95% confidence interval(Cl):2.21-7.14;42.5% vs 8.6%,P=1.72×10-19 OR=13.62,95% CI:7.16-25.9;22.9% vs 8.1%,P=4.64×106,OR=4.1,95% CI:2.25-7.47].Only rs1055348 showed a significantly higher frequency in the PM-DILI group than in the other-DILI group(42.5% vs 13.6%,P=1.84×10-10,OR=10.06,95% Cl:5.06-20.0),which suggested that it is a specific risk factor for PM-DILI.rs1055348 may become a tag for HLA-B*35:01 with 100% sensitivity and 97.7% specificity in the PM-DILI group and 100% sensitivity and 98.1% specificity in the other-DILI group.Furthermore,HLA-B*35:01 was confirmed to be associated with PM-DILI with a frequency of 41.1% in the PM-DILI group compared with 11.9%(P=4.30×10-11,OR=11.11,95% CI:5.57-22.19) in the other-DILI group and 2.7%(P=6.22×10-166,OR=62.62,95% Cl:35.91-109.20) in the Han-MHC database.CONCLUSION rslll686806,rs1055348,and rs202047044 are associated with PM-DILI,of which,rs1055348 is specific to PM-DILI.As a tag for HLA-B*35:01,rs1055348 may become an alternative predictive biomarker of PM-DILI.展开更多
Objective To analyze the role of resistin in insulin resistance (IR) through investigating the variation of plasma resistin levels and single-nucleotide polymorphisms (SNPs) in resistin gene 5’ flanking region in str...Objective To analyze the role of resistin in insulin resistance (IR) through investigating the variation of plasma resistin levels and single-nucleotide polymorphisms (SNPs) in resistin gene 5’ flanking region in stroke patients.Methods In 103 atherothrombotic cerebral infarction (ACI) patients, 85 lacunar infarction (LI) patients, 70 intracerebral hemorrhage (ICH) patients, and 86 healthy controls, plasma resistin and insulin levels were measured by ELISA , SNPs in resistin gene 5’ flanking region were detected by PCR and direct DNA sequencing. The subjects’ body height and weight, the body mass index, quantitative insulin sensitivity check index (QUICKI), blood pressure, and the concentration of fasting plasma glucose, triglyceride, total cholesterol, creatinine, low-density lipoprotein, and high-density lipoprotein were also determined. Results QUICKI was significantly lower in the ACI and ICH patients (0.316±0.037 and 0.309±0.032, respectively) than that in the controls (0.342±0.043, P<0.001), while plasma resistin level was significantly higher in the ACI and ICH patients (6.36±3.79 and 7.15±4.27 ng/mL, respectively) than that in the controls (5.28±2.56 ng/mL, P<0.05), but such difference was not observed in the LI patients compared with controls. There was a statistically negative correlation between plasma resistin level with QUICKI (r=-0.228, P<0.001). The distributions of allele and genotype frequencies of resistin gene -420C>G and -537A>C SNPs were not significantly different among the different groups, and those SNPs were not correlated with other clinical and biochemical parameters.Conclusions Plasma resistin is associated with stroke by participating in the development of IR. The SNPs in resistin gene 5’ flanking region has no impact on the plasma resistin level.展开更多
Beef from Japanese Black cattle (JBK), is popular in Japan and valued for its highly marbled fat content. In JBK, genes affecting oleic acid content in meat have been studied mainly to lower the fat melting point and ...Beef from Japanese Black cattle (JBK), is popular in Japan and valued for its highly marbled fat content. In JBK, genes affecting oleic acid content in meat have been studied mainly to lower the fat melting point and improve tenderness;however, there has been no direct correlation demonstrated between beef taste and oleic acid. To investigate genes affecting other fatty acids other than oleic acid, polymorphisms of the fatty acid desaturase 2 (FADS2) gene were genotyped and associations with fatty acid profile in JBK beef were investigated. Amplifications of 5’-flanking regions, 12 exons, and 3’-untranslated regions of the FADS2 gene in three Japanese and five Western cattle breeds via PCR, were amplified, sequenced and SNPs were identified using specific TaqMan genotyping assay. Fatty acid composition of intramuscular adipose tissue of the Trapezius muscle was analyzed in JBK steers. Six of the 15 identified SNPs are novel and have never been registered in any public bovine SNP database. A non-synonymous SNP (rs211580559;C > T;294 Ala > Val) in exon 7 was examined in order to evaluate its association with fatty acid profiles. The data showed that highly significant association existed between rs211580559 and C18:2 (n-6) composition, and accounted for 22.3% of the variation. There were no significant relationships between rs2115-80559 and the other fatty acids. It was concluded that rs211580559 of the FADS2 gene may be a useful selection marker for reducing unfavorable volatiles generated from linoleic acid in JBK beef during the cooking process.展开更多
Our previous studies have demonstrated that ceruloplasmin （CP） dysmetabolism is correlated with Parkinson＇s disease （PD）. However, the causes of decreased serum CP levels in PD patients remain to be clarified. Th...Our previous studies have demonstrated that ceruloplasmin （CP） dysmetabolism is correlated with Parkinson＇s disease （PD）. However, the causes of decreased serum CP levels in PD patients remain to be clarified. This study aimed to explore the potential association between genetic variants of the CP gene and PD. Clinical features, serum CP levels, and the CP gene （both promoter and coding regions） were analyzed in 60 PD patients and 50 controls. A luciferase reporter system was used to investigate the function of promoter single-nucleotide polymorphisms （SNPs）. High-density comparative genomic hybridization microarrays were also used to detect large-scale copy-number variations in CP and an additional 47 genes involved in PD and/or copper/ iron metabolism. The frequencies of eight SNPs （one intronic SNP and seven promoter SNPs of the CP gene） and their haplotypes were significantly different between PD patients, especially those with lowered serum CP levels, and controls. However, the luciferase reporter system revealed no significant effect of the risk haplotype on promoter activity of the CP gene. Neither these SNPs nor their haplotypes were correlated with the Hoehn and Yahr staging of PD. The results of this study suggest that common genetic variants of CP are associated with PD and further investigation is needed to explore their functions in PD.展开更多
Background: Identification of risk genes and loci associated with the recurrence and metastasis of breast cancer (BC) is ofutmost importance. Genome-wide association studies (GWASs) represent valuable tools for identi...Background: Identification of risk genes and loci associated with the recurrence and metastasis of breast cancer (BC) is ofutmost importance. Genome-wide association studies (GWASs) represent valuable tools for identifying the disease risk associated with a given single-nucleotide polymorphism (SNP);they offer significant insights into the disease progression mechanism by analyzing SNP information of the entire genome. Though GWAS has already identified several genetic susceptibilitySNPs for BC, their significance in the recurrence and metastasis of this cancer remains unclear. Here, we used a GWASapproach to identify SNPs specifically associated with the risk of BC recurrence and metastasis.Methods: This study adopted a two-stage GWAS approach. In the first stage, 97 pairs of BC patients with or without recurrenceand metastasis, treated at the Shandong Cancer Hospital and Institute from November 2013 to April 2014, were identified usingpropensity score matching. DNA extracted from the patient peripheral blood was then subjected to Illumina ASA chip analysisfor genome-wide SNP detection. In the second stage, the findings were verified in a validation set of 854 BC patients recruited atthe same hospital from May 2014 to June 2015. SNP genotyping was performed using time-of-flight mass spectrometry. The SNPloci and their corresponding genes and pathways were analyzed using the DAVID (https://david.ncifcrf.gov/) online enrichment analysis tool.Results: Based on the GWAS results, 191 SNP-related genes significantly associated with BC recurrence and metastasis wereidentified as expression quantitivative trait loci (p < 0.001). Functional and pathway enrichment analyses subsequently revealedthe potential involvement of glutamatergic synaptic transmission, calcium signaling, and insulin secretion pathways in BCrecurrence and metastasis. Based on genotype correlation and database expression levels, rs10108514, rs12920540, rs4273077,and rs4730155 were found to be significantly associated with the risk of BC recurrence and metastasis.Conclusion: Our study suggests that the SNPs rs10108514, rs12920540, rs4273077, and rs4730155 are correlated with the risk ofBC recurrence and metastasis, potentially by being implicated in glutamatergic synaptic transmission, calcium signaling, andinsulin secretion pathways.展开更多
Two common polymorphisms of the peroxisome proliferator-activated receptor gamma(PPARG) gene, rs1801282 and rs3856806, may be important candidate gene loci affecting the susceptibility to ischemic stroke. This case-co...Two common polymorphisms of the peroxisome proliferator-activated receptor gamma(PPARG) gene, rs1801282 and rs3856806, may be important candidate gene loci affecting the susceptibility to ischemic stroke. This case-control study sought to identify the relationship between these two single-nucleotide polymorphisms and ischemic stroke risk in a northern Chinese Han population. A total of 910 ischemic stroke participants were recruited from the First Hospital of China Medical University, Shenyang, China as a case group, of whom 895 completed the study. The 883 healthy controls were recruited from the Health Check Center of the First Hospital of China Medical University, Shenyang, China. All participants or family members provided informed consent. The study protocol was approved by the Ethics Committee of the First Hospital of China Medical University, China on February 20, 2012(approval No. 2012-38-1). The protocol was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR-COC-17013559). Plasma genomic DNA was extracted from all participants and analyzed for rs1801282 and rs3856806 single nucleotide polymorphisms using a SNaPshot Multiplex sequencing assay. Odds ratios(ORs) and 95% confidence intervals(CIs) were calculated using unconditional logistic regression to estimate the association between ischemic stroke and a particular genotype. Results demonstrated that the G allele frequency of the PPARG gene rs1801282 locus was significantly higher in the case group than in the control group(P < 0.001). Individuals carrying the G allele had a 1.844 fold increased risk of ischemic stroke(OR = 1.844, 95% CI: 1.286–2.645, P < 0.001). Individuals carrying the rs3856806 T allele had a 1.366 fold increased risk of ischemic stroke(OR = 1.366, 95% CI: 1.077–1.733, P = 0.010). The distribution frequencies of the PPARG gene haplotypes rs1801282-rs3856806 in the control and case groups were determined. The frequency of distribution in the G-T haplotype case group was significantly higher than that in the control group. The risk of ischemic stroke increased to 2.953 times in individuals carrying the G-T haplotype(OR = 2.953, 95% CI: 2.082–4.190, P < 0.001). The rs1801282 G allele and rs3856806 T allele had a multiplicative interaction(OR = 3.404, 95% CI: 1.631–7.102, P < 0.001) and additive interaction(RERI = 41.705, 95% CI: 14.586–68.824, AP = 0.860;95% CI: 0.779–0.940;S = 8.170, 95% CI: 3.772–17.697) on ischemic stroke risk, showing a synergistic effect. Of all ischemic stroke cases, 86% were attributed to the interaction of the G allele of rs1801282 and the T allele of rs3856806. The effect of the PPARG rs1801282 G allele on ischemic stroke risk was enhanced in the presence of the rs3856806 T allele(OR = 8.001 vs. 1.844). The effect of the rs3856806 T allele on ischemic stroke risk was also enhanced in the presence of the rs1801282 G allele(OR = 2.546 vs. 1.366). Our results confirmed that the G allele of the PPARG gene rs1801282 locus and the T allele of the rs3856806 locus may be independent risk factors for ischemic stroke in the Han population of northern China, with a synergistic effect between the two alleles.展开更多
AIM: To explore the associations of polymorphisms of lipopolysaccharide binding protein (LBP), cluster of differentiation 14 (CD14), toll-like receptor 4 (TLR-4), interleukin-6 (IL-6) and tumor necrosis factor α (TNF...AIM: To explore the associations of polymorphisms of lipopolysaccharide binding protein (LBP), cluster of differentiation 14 (CD14), toll-like receptor 4 (TLR-4), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) with the colorectal carcinoma (CRC) risk in Han Chinese. METHODS: Polymorphisms of LBP (rs1739654, rs223 2596, rs2232618), CD14 (rs77083413, rs4914), TLR-4 (rs5030719), IL-6 (rs13306435) and TNF-α (rs35131721) were genotyped in 479 cases of sporadic colorectal carcinoma and 486 healthy controls of Han Chinese in a case-control study. Single-nucleotide polymorphisms (SNPs) between cases and controls were analyzed by unconditional logistic regression. RESULTS: GA and GG genotypes of LBP rs2232596 were associated with a significantly increased risk ofCRC [odds ratio (OR) = 1.51, 95% confidence interval (CI) 1.15-1.99, P = 0.003; OR = 2.49, 95% CI 1.16-5.38, P = 0.016, respectively]. A similar association was also observed for the CG genotype of CD14 rs4914 (OR= 1.69, 95% CI 1.20-2.36, P = 0.002). In addition, a combination of polymorphisms in LBP rs2232596 and CD14 rs4914 led to a 3.4-fold increased risk of CRC (OR = 3.44, 95% CI 1.94-6.10, P = 0.000). CONCLUSION: This study highlights the LBP rs2232596 and CD14 rs4914 polymorphisms as biomarkers for elevated CRC susceptibility in the Chinese Han population.展开更多
Single-nucleotide polymorphisms in the brain-derived neurotrophic factor gene may affect the secretion and function of brain-derived neurotrophic factor, thereby affecting the occurrence, severity and prognosis of isc...Single-nucleotide polymorphisms in the brain-derived neurotrophic factor gene may affect the secretion and function of brain-derived neurotrophic factor, thereby affecting the occurrence, severity and prognosis of ischemic stroke. This case-control study included 778 patients (475 males and 303 females, mean age of 64.0 ± 12.6 years) in the acute phase of ischemic stroke and 865 control subjects (438 males and 427 females, mean age of 51.7 ± 14.7 years) from the Department of Neurology, Wes: China Hospital, Sichuan University, China between September 2011 and December 2014. The patients' severities of neurological defici:s in the acute phase were assessed using the National Institutes of Health Stroke Scale immediately after admission to hospital. The ischemic stroke patients were divided into different subtypes according to the Trial of Org 10172 in Acute Stroke Treatment classification. Early prognosis was evaluated using the Modified Rankin Scale when the patients were discharged. Genomic DNA was extracted from peripheral blood of participants. Genotyping of rs7124442 and rs6265 was performed using Kompetitive Allele Specific polymerase chain reaction genotyping technology. Our results demonstrated that patients who carried the C allele of the rs7124442 locus had a lower risk of poor prognosis than the T allele carriers (odds ratio [OR]= 0.67;95% confidence interval [CI]: 0.45-1.00;P = 0.048). The patients with the CC or TC genotype also exhibited lower risk than TT carriers (OR = 0.65;95% CI: 0.42-1.00;P = 0.049). The AA genotype at the rs6265 locus was associated with the occurrence of ischemic stroke in patients with large-artery atherosclerosis (OR = 0.5& 95% CI: 0.37-0.90;P = 0.015). We found that the C allele (CC and TC genotypes) at the rs7124442 locus may be protective for the prognosis of ischemic stroke. The AA genotype at the rs6265 locus is likely a protective factor against the occurrence of ischemic stroke in patients with large-artery atherosclerosis. The study protocol was approved by the Ethics Committee of West China Hospital of Sichuan University, China (approval ID number 2008,4]) on July 25, 2008.展开更多
BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bo...BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bowel syndrome(IBS).AIM To assess the association of HTR3 polymorphisms with depressive,anxiety,and somatization symptoms in individuals with IBS.METHODS In this retrospective study,623 participants with IBS were recruited from five specialty centers in Germany,Sweden,the United States,the United Kingdom,and Ireland.Depressive,anxiety,and somatization symptoms and sociodemographic characteristics were collected.Four functional SNPs—HTR3A c.-42C>T,HTR3B c.386A>C,HTR3C c.489C>A,and HTR3E c.*76G>A—were genotyped and analyzed using the dominant and recessive models.We also performed separate analyses for sex and IBS subtypes.SNP scores were calculated as the number of minor alleles of the SNPs above.The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays.RESULTS Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model(F_(depressive)=7.475,P_(depressive)=0.006;F_(anxiety)=6.535,P_(anxiety)=0.011).A higher SNP score(range 0-6)was linked to a worsened depressive symptoms score(F=7.710,P-linear trend=0.006)in IBS.The potential relevance of the HTR3C SNP was corroborated,showing changes in the expression level of 5-HT3AC variant receptors.CONCLUSION We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS.The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.展开更多
Objective The aim of this study is to establish whether cyclin-dependent kinase inhibitor 2B antisense RNA 1(CDKN2 B-AS1) gene polymorphisms are associated with premature triple-vessel disease(PTVD). Methods Nine sing...Objective The aim of this study is to establish whether cyclin-dependent kinase inhibitor 2B antisense RNA 1(CDKN2 B-AS1) gene polymorphisms are associated with premature triple-vessel disease(PTVD). Methods Nine single-nucleotide polymorphisms(rs1063192, rs10757274, rs1333042, rs1333049, rs2285327, rs3217986, rs3217992, rs4977574, and rs9632884) were genotyped in 884 PTVD patients and 907 control subjects(males ≤ 50 years old and females ≤ 60 years old) using the improved multiplex ligase detection reaction method. Results The allele frequencies of rs10757274 G, rs1333049 C, rs4977574 G(all P < 0.001), and rs3217986 G(P = 0.040) were significantly higher in the PTVD group than in the control group, but those of rs1063192 A, rs1333042 G, and rs9632884 C(all P < 0.001) were significantly lower in the former than in the latter. Logistic regression analysis revealed that homozygote AA of rs1333042 is associated with decreased risk for PTVD(OR = 0.42, 95% CI: 0.22-0.82, P = 0.011). In addition, the allele frequencies observed differed between genders. The G allele of rs3217986 was associated with increased risk for PTVD in male patients only(OR = 2.94, 95% CI: 1.27-6.80, P = 0.012) in the dominant model, and no positively mutated allele was found in female patients. Conclusion Polymorphisms of the CDKN2 B-AS1 gene are associated with the incidence of PTVD in the Chinese population. Furthermore, the frequencies of mutated alleles differed between genders.展开更多
AIM To evaluate associations between mi RNA target genes IL12B,INSR,CCND1 and IL10 polymorphisms and gastric cancer(GC)in European population.METHODS Gene polymorphisms were analyzed in 508 controls and474 GC patients...AIM To evaluate associations between mi RNA target genes IL12B,INSR,CCND1 and IL10 polymorphisms and gastric cancer(GC)in European population.METHODS Gene polymorphisms were analyzed in 508 controls and474 GC patients from 3 tertiary centers in Germany,Lithuania and Latvia.Controls were patients from the out-patient departments,who were referred for upper endoscopy because of dyspeptic symptoms and had no history of previous malignancy.Gastric cancer(GC)patients had histopathological verification of gastric adenocarcinoma.Genomic DNA was extracted using salting out method from peripheral blood mononuclear cells.IL12B T>G(rs1368439),INSR T>C(rs1051690),CCND1 A>C(rs7177)and IL10 T>C(rs3024498)SNPs were genotyped by the real-time polymerase chain reaction.Associations between gene polymorphism and GC were evaluated using multiple logistic regression analysis with adjustment for sex,age and country of birth.RESULTS We observed similar distribution of genotypes and allelic frequencies of all polymorphisms between GC patients and controls except of INSR rs1051690.The frequency of the T allele of INSR gene was significantly higher in GC patients than in controls(23.26%and 19.19%respectively,P=0.028).CT genotype was also more prevalent in patients compared to control group(38.48%and 30.12%respectively,P<0.021).Logistic regression analysis revealed that only one polymorphism(rs1051690 in INSR gene)was associated with increased risk of GC.Carriers of CT genotype had higher odds of GC when compared to CC genotype(OR=1.45,95%PI:1.08-1.95,P=0.01).Similar association was observed in a dominant model for INSR gene,where comparison of TT+CT vs CC genotypes showed an increased risk of GC(OR=1.44,95%PI:1.08-1.90,P=0.01).Other analyzed SNPs were not associated with the presence of GC.CONCLUSION INSR rs1051690 SNP is associated with increased risk of GC,while polymorphisms in IL12B,CCND1 and IL10genes are not linked with the presence of GC.展开更多
TSSK6 is a member of the testis-specific serine/threonine kinase family. Male Tssk6 knockout mice are infertile owing to sperrnatogenic impairment,including sperm count reduction,a decrease in motile sperm number and ...TSSK6 is a member of the testis-specific serine/threonine kinase family. Male Tssk6 knockout mice are infertile owing to sperrnatogenic impairment,including sperm count reduction,a decrease in motile sperm number and motility rates,and an increase in the number of sperms with abnormal morphology. We investigated the possible association between variations oftbe TSSK6 gene and spermatogenic impairment in humans. Mutation screening of TSSK6 was carried out in 519 patients with azoospermia （n = 273） or severe oligozoospermia （n = 246） and in 359 controls with normozoospermia by denaturing high-performance liquid chromatography and DNA sequencing. The frequencies of alleles and genotypes of gene polymorphism were compared between patients and controls. A novel triallelic polymorphism in TSSK6,c.822＋126T〉G/C,was identified. The frequencies of genotype TT and allele T were increased dramatically in infertile patients compared with controls,whereas genotype TG,allele G and allele C frequencies were significantly higher in controls than in patients. Further study revealed that the allele C frequency of controls was remarkably higher than that of patients with oligospermia. Our findings,for the first time,suggested an association of c.822＋I26T〉G/C in TSSK6 with spermatogenic impairment in humans in which allele T may be a risk factor for male infertility,while alleles C and G may decrease susceptibility to male infertility.展开更多
Objective To investigate the association between two polymorphisms of follicle stimulating hormone receptor （FSHR） gene and polycystic ovary syndrome （PCOS） susceptibility. Methods Case-control studies on relatio...Objective To investigate the association between two polymorphisms of follicle stimulating hormone receptor （FSHR） gene and polycystic ovary syndrome （PCOS） susceptibility. Methods Case-control studies on relationship of Thr307Ala and Asn680Ser polymorphisms in FSHR gene and PCOS susceptibility were searched from PubMed, ISI web of knowledge, EBSCO, and China National Knowledge Infrastructure （CNKI） databases up to March 21, 2013. The pooled odds ratio （OR） and 95% confidence interval （CO were calculated using fixed- or random-effect model based on heterogeneity test in 5 genotype models analyses. Results A total of 11 studies were included in the Meta-analysis. The random-effect analysis showed Asn680Ser was significantly associated with the reduced susceptibility to PCOS with dominant model （Asn/Asn＋Asn/Ser vs. Ser/Ser, OR=0.83, 95% CI： 0.69-1.00）, recessive model （Asn/Asn vs. Asn/Ser＋ Ser/Ser, OR=0.84, 95% CI： 0.72-0.98）, homozygote comparison （Ash/Ash vs. Ser/Ser, 0R=0.79, 95% CI： 0.63-0.98）, and the allele contrast （Asn vs. Ser, OR=0.87, 95% CI： 0.79-0.97） respectively（P=0.02, I2=56.0%）, being protective factors for PCOS. However, no significant associations were found between Thr307Ala and PCOS. Conclusion There might be a significant association between Asn680Ser polymorphism and PCOS.展开更多
Variants at the GTF2I repeat domain containing 1(GTF2IRD1)–GTF2I locus are associated with primary Sj?gren's syndrome, systemic lupus erythematosus, and rheumatoid arthritis. Numerous studies have indicated that ...Variants at the GTF2I repeat domain containing 1(GTF2IRD1)–GTF2I locus are associated with primary Sj?gren's syndrome, systemic lupus erythematosus, and rheumatoid arthritis. Numerous studies have indicated that this susceptibility locus is shared by multiple autoimmune diseases. However, until now there were no studies of the correlation between GTF2IRD1–GTF2I polymorphisms and neuromyelitis optica spectrum disorders(NMOSD). This case control study assessed this association by recruiting 305 participants with neuromyelitis optica spectrum disorders and 487 healthy controls at the Department of Neurology, from September 2014 to April 2017. Peripheral blood was collected, DNA extracteds and the genetic association between GTF2IRD1–GTF2I polymorphisms and neuromyelitis optica spectrum disorders in the Chinese Han population was analyzed by genotyping. We found that the T allele of rs117026326 was associated with an increased risk of neuromyelitis optica spectrum disorders(odds ratio(OR) = 1.364, 95% confidence interval(CI) 1.019–1.828; P = 0.037). This association persisted after stratification analysis for aquaporin-4 immunoglobulin G antibodies(AQP4-IgG) positivity(OR = 1.397, 95% CI 1.021–1.912; P = 0.036) and stratification according to coexisting autoimmune diseases(OR = 1.446, 95% CI 1.072–1.952; P = 0.015). Furthermore, the CC genotype of rs73366469 was frequent in AQP4-IgG-seropositive patients(OR = 3.15, 95% CI 1.183–8.393, P = 0.022). In conclusion, the T allele of rs117026326 was associated with susceptibility to neuromyelitis optica spectrum disorders, and the CC genotype of rs73366469 conferred susceptibility to AQP4-IgG-seropositivity in Han Chinese patients. The protocol was approved by the Ethics Committee of West China Hospital of Sichuan University, China(approval number: 2016-31) on March 2, 2016.展开更多
Objective: To investigate the association between TLR3 and TLR7 polymorphisms with susceptibility and clinical manifestations of Chikungunya Fever.Methods: A total of 177 individuals were studied: 73 patients with a c...Objective: To investigate the association between TLR3 and TLR7 polymorphisms with susceptibility and clinical manifestations of Chikungunya Fever.Methods: A total of 177 individuals were studied: 73 patients with a confirmed diagnosis for Chikungunya virus and 104 non-infected individuals. Polymorphisms were determined by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism(PCR-RFLP).Results: Our analysis showed an increased CC genotype frequency of the TLR7 rs3853839 polymorphism in male patients compared to control(29% versus 2%,respectively; OR=20.69; 95% CI=2.55-167.36; P<0.001). Furthermore,arthritis(acute and chronic) was frequently found in CC male patients. On the contrary,65% of CG carriers were no-infected males(29% versus 65%,respectively; OR=0.23,95% CI=0.48-3.04; P=0.002). Finally,we observed a higher frequency of lymphopenia in CG male patients(CG=666.86±233.77,GG=1,314.27±752.29 cells/mm3,P=0.047). Conclusions: Our results suggest the TLR7 rs3853839 polymorphism is associated with lymphopenia and increased susceptibility to Chikungunya Fever in males.展开更多
AIM To investigate the contribution of polymorphisms in the CYP1A1, CYP2E1 and EPHX1 genes on sporadic colorectal cancer(SCRC) risk. METHODS Six hundred forty-one individuals(227 patients with SCRC and 400 controls) w...AIM To investigate the contribution of polymorphisms in the CYP1A1, CYP2E1 and EPHX1 genes on sporadic colorectal cancer(SCRC) risk. METHODS Six hundred forty-one individuals(227 patients with SCRC and 400 controls) were enrolled in the study. The variables analyzed were age, gender, tobacco and alcohol consumption, and clinical and histopathological tumor parameters. The CYP1A1 *2A, CYP1A1 *2C CYP2E1 *5B and CYP2E1 *6 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). The EPHX1 Tyr113 His, EPHX1 His139 Arg and CYP1A1 *2C polymorphisms were detected by real-time PCR. Chisquared test and binary logistic regression were used in the statistical analysis. Haplotype analysis was conducted using the Haploview program, version 2.05.RESULTS Age over 6 2 years was a risk factor for SCRC development(OR = 7.54, 95%CI: 4.94-11.50, P < 0.01). Male individuals were less susceptible to SCRC(OR = 0.55, 95%CI: 0.35-0.85, P < 0.01). The CYP2E1*5B polymorphism was associated with SCRC in the codominant(heterozygous genotype: OR = 2.66, 95%CI: 1.64-4.32, P < 0.01), dominant(OR = 2.82, 95%CI: 1.74-4.55, P < 0.01), overdominant(OR = 2.58, 95%CI: 1.59-4.19, P < 0.01), and log-additive models(OR = 2.84, 95%CI: 1.78-4.52, P < 0.01). The CYP2E1*6 polymorphism was associated with an increased SCRC risk in codominant(heterozygous genotype: OR = 2.81, 95%CI: 1.84-4.28, P < 0.01; homozygous polymorphic : OR = 7. 3 2, 9 5 % C I : 1.85-28.96, P < 0.01), dominant(OR = 2.97, 95%CI: 1.97-4.50, P < 0.01), recessive(OR = 5.26, 95%CI: 1.35-20.50, P = 0.016), overdominant(OR = 2.64, 95%CI: 1.74-4.01, P < 0.01), and log-additive models(OR = 2.78, 95%CI: 1.91-4.06, P < 0.01). The haplotype formed by the minor alleles of the CYP2E1*5B(C) and CYP2E1*6(A) polymorphisms was associated with SCRC(P = 0.002). However, the CYP1A1 *2A, CYP1A1 *2C, EPHX1 Tyr113 His and EPHX1 His139 Arg polymorphisms were not associated with SCRC.CONCLUSION In conclusion, the results demonstrated that CYP2E1*5B and CYP2E1*6 minor alleles play a role in the development of SCRC.展开更多
Objective： A study in a Caucasian population has identified two single-nucleotide polymorphisms （SNPs） in ZNF533, one in DOCK4, and two in IMMP2L, which were all significantly associated with autism. They are locat...Objective： A study in a Caucasian population has identified two single-nucleotide polymorphisms （SNPs） in ZNF533, one in DOCK4, and two in IMMP2L, which were all significantly associated with autism. They are located in AUTS1 and AUTS5, which have been identified as autism susceptibility loci in several genome-wide screens. The present study aimed to investigate whether ZNF533, DOCK4, and IMMP2L genes are also associated with autism in a northeastern Chinese Han population. Methods： We performed a similar association study using families with three individuals （one autistic child and two unaffected parents）. A family-based transmission disequilibrium test （TDT） was used to analyze the results. Results： There were significant associations between autism and the two SNPs of ZNF533 gene （rs11885327： X^2=4.5200, P=0.0335; rs1964081 ：）（2=4.2610, P=0.0390） and the SNP of DOCK4 gene （rs2217262 X^2=5.3430, P=0.0208）. Conclusions： Our data suggest that ZNF533 and DOCK4 genes are linked to a predisposition to autism in the northeastern Chinese Han population.展开更多
基金funded by the National Natural Science Foundation of China(grant no.32270238 and 31870311).
文摘Subtropical evergreen broad-leaved trees are usually vulnerable to freezing stress,while hexaploid wild Camellia oleifera shows strong freezing tolerance.As a valuable genetic resource of woody oil crop C.oleifera,wild C.oleifera can serve as a case for studying the molecular bases of adaptive evolution to freezing stress.Here,47 wild C.oleifera from 11 natural distribution sites in China and 4 relative species of C.oleifera were selected for genome sequencing.“Min Temperature of Coldest Month”(BIO6)had the highest comprehensive contribution to wild C.oleifera distribution.The population genetic structure of wild C.oleifera could be divided into two groups:in cold winter(BIO6≤0℃)and warm winter(BIO6>0℃)areas.Wild C.oleifera in cold winter areas might have experienced stronger selection pressures and population bottlenecks with lower N_(e) than those in warm winter areas.155 singlenucleotide polymorphisms(SNPs)were significantly correlated with the key bioclimatic variables(106 SNPs significantly correlated with BIO6).Twenty key SNPs and 15 key copy number variation regions(CNVRs)were found with genotype differentiation>50%between the two groups of wild C.oleifera.Key SNPs in cis-regulatory elements might affect the expression of key genes associated with freezing tolerance,and they were also found within a CNVR suggesting interactions between them.Some key CNVRs in the exon regions were closely related to the differentially expressed genes under freezing stress.The findings suggest that rich SNPs and CNVRs in polyploid trees may contribute to the adaptive evolution to freezing stress.
基金National Key Research and Development Program for Young scientists,Grant/Award Number:2021YFF0703200National Natural Foundation Joint Fund for Regional Innovation and Development,Grant/Award Number:U21A20194+1 种基金National Natural Science Foundation of China,Grant/Award Number:32170540National Key Research and Development Program,Grant/Award Number:2022YFF0711005。
文摘Chinese hamster with Chinese characteristics is used in experiments,and it is of great value in the field of medical biology research.However,at present,there is no high-efficiency method for evaluating the genetic quality of Chinese hamsters.Here,we developed a novel Chinese hamster genetic quality detection system using single-nucleotide polymorphism(SNP)markers.To find SNP loci,we conducted whole genome sequencing on 24 Chinese hamsters.Then,we employed an SNP locus screening criterion that we set up previously and initially screened 214 SNP loci with wide genome distribution and high polymorphism level.Subsequently,we developed the SNP detection system using a multitarget region capture technique based on second-generation sequencing,and a 55 SNP panel for genetic evaluation of Chinese hamster populations was developed.PopGen.32.analysis results showed that the average effective allele number,Shannon index,observed heterozygosity,expected heterozygosity,average heterozygosity,polymorphism information,and other genetic parameters of Chinese hamster population A were higher than those in population B.Using scientific screening and optimization,we successfully developed a novel Chinese hamster SNP genetic detection system that can efficiently and accurately analyze the genetic quality of the Chinese hamster population.
基金ACKNOWLEDGMENTS This research was supported by the Major State Basic Research Development Program of China （973 Program, Noso 2006GB504005 and 2009CB941700）, the National Natural Science Foundation of China （No. 30872765） and the Basic Research Key Program of Shanghai （10]C1410800）. Shi-Wei Duan is sponsored partly by the K. C. Wong Magna Fund of Ningbo University. Wethank Dr Ching-Ling Chen for kind suggestions regarding English in drafting this paper.
文摘Multiplex polymerase chain reaction （PCR） has been widely used to detect Y-chromosome micredeletions, which is one of the major causes of male infertility. Both the European Academy of Andrology （EAA） and the European Molecular Genetics Quality Network （EMQN） have recommended the use of sY84 and sY86 markers for the detection of azoospermia factor a （AZFa） microdeletion during DNA testing for male infertility. In this study, a large-scale analysis of AZF microdeletion in a total of 630 Chinese males, including healthy semen donors （n=200）, infertile males with normal sperm count （n=226） and patients with either nonobstructive azoospermia or severe oligozoospermia （n=204）, was performed. A series of nine sequence-tagged site （STS） markers from the AZF region of the Y chromosome was used to detect microdeletions. All primers were designed based on the recommendations of the National Center for Biotechnology Information. An unusually high incidence （73/630, 11.6%） of sY84-absent but sY86-present genotypes was observed in the AZFa microdeletion screening. Sequencing the sY84-flanking region revealed a total of 73 patients with sY84-absent but sY86-present genotypes have a T-to-G transversion at the fifth base from the 5＇ end of the reverse sY84 primer. These prevalent false positives, which were not only observed in infertile men, but also observed in donors, resulted from a single-nucleotide polymorphism （SNP） named rs72609647 in the targeting sequence of the reverse sY84 primer. Our study suggests that a pre-screening of existence of rs72609647 polymorphism can prevent the frequent false positive results of AZFa microdeletions detection in the infertile Chinese males. Given the SNP rs72609647 was recently found in a deep sequencing of a Chinese individual, the current EAA and EMQN standards may need to be scrutinized among different populations to avoid the potential genetic variations in the primer binding sequences.
基金the National Natural Science Foundation of China,No.81470849the China Mega-Project for Infectious Diseases,No.2017ZX10203202.
文摘BACKGROUND Polygonum multiflorum is one of the leading causes of herb-induced liver injury in China.HLA-B*35:01 is reported to be a potential biomarker of Polygonum multiflorum-induced liver injury(PM-DILI).However,little is known about the relationship between single-nucleotide polymorphisms(SNPs) and PM-DILI.AIM To identify SNPs that indicate susceptibility to PM-DILI METHODS We conducted a systematic study enrolling 382 participants from four independent hospitals,including 73 PM-DILI patients,118 patients with other drug-induced liver injury(other-DILI) and 191 healthy controls.Whole-exome sequencing was performed for 8 PM-DILI patients and 8 healthy controls who were randomly selected from the above subjects.Nineteen SNPs that showed high frequencies in the 8 PM-DILI patients were selected as candidate SNPs and then screened in 65 PM-DILI patients,118 other-DILI patients and 183 healthy controls using the MassARRAY system.HLA-B high-resolution genotyping was performed for the 73 PM-DILI and 118 other-DILI patients.The Han-MHC database was selected as a population control for HLA-B analysis.P <6.25 x 103 after Bolferroni correction was considered significant.RESULTS The frequencies of rslll686806 in the HLA-A gene,rs1055348 in the HLA-B gene,and rs202047044 in the HLA-DRB1 gene were significantly higher in the PM-DILI group than in the control group [27.2% vs 11.6%,P=1.72×105,odds ratio(OR)=3.96,95% confidence interval(Cl):2.21-7.14;42.5% vs 8.6%,P=1.72×10-19 OR=13.62,95% CI:7.16-25.9;22.9% vs 8.1%,P=4.64×106,OR=4.1,95% CI:2.25-7.47].Only rs1055348 showed a significantly higher frequency in the PM-DILI group than in the other-DILI group(42.5% vs 13.6%,P=1.84×10-10,OR=10.06,95% Cl:5.06-20.0),which suggested that it is a specific risk factor for PM-DILI.rs1055348 may become a tag for HLA-B*35:01 with 100% sensitivity and 97.7% specificity in the PM-DILI group and 100% sensitivity and 98.1% specificity in the other-DILI group.Furthermore,HLA-B*35:01 was confirmed to be associated with PM-DILI with a frequency of 41.1% in the PM-DILI group compared with 11.9%(P=4.30×10-11,OR=11.11,95% CI:5.57-22.19) in the other-DILI group and 2.7%(P=6.22×10-166,OR=62.62,95% Cl:35.91-109.20) in the Han-MHC database.CONCLUSION rslll686806,rs1055348,and rs202047044 are associated with PM-DILI,of which,rs1055348 is specific to PM-DILI.As a tag for HLA-B*35:01,rs1055348 may become an alternative predictive biomarker of PM-DILI.
基金"135 Project"Key Talent Fund of Public Health Department of Jiangsu Province
文摘Objective To analyze the role of resistin in insulin resistance (IR) through investigating the variation of plasma resistin levels and single-nucleotide polymorphisms (SNPs) in resistin gene 5’ flanking region in stroke patients.Methods In 103 atherothrombotic cerebral infarction (ACI) patients, 85 lacunar infarction (LI) patients, 70 intracerebral hemorrhage (ICH) patients, and 86 healthy controls, plasma resistin and insulin levels were measured by ELISA , SNPs in resistin gene 5’ flanking region were detected by PCR and direct DNA sequencing. The subjects’ body height and weight, the body mass index, quantitative insulin sensitivity check index (QUICKI), blood pressure, and the concentration of fasting plasma glucose, triglyceride, total cholesterol, creatinine, low-density lipoprotein, and high-density lipoprotein were also determined. Results QUICKI was significantly lower in the ACI and ICH patients (0.316±0.037 and 0.309±0.032, respectively) than that in the controls (0.342±0.043, P<0.001), while plasma resistin level was significantly higher in the ACI and ICH patients (6.36±3.79 and 7.15±4.27 ng/mL, respectively) than that in the controls (5.28±2.56 ng/mL, P<0.05), but such difference was not observed in the LI patients compared with controls. There was a statistically negative correlation between plasma resistin level with QUICKI (r=-0.228, P<0.001). The distributions of allele and genotype frequencies of resistin gene -420C>G and -537A>C SNPs were not significantly different among the different groups, and those SNPs were not correlated with other clinical and biochemical parameters.Conclusions Plasma resistin is associated with stroke by participating in the development of IR. The SNPs in resistin gene 5’ flanking region has no impact on the plasma resistin level.
文摘Beef from Japanese Black cattle (JBK), is popular in Japan and valued for its highly marbled fat content. In JBK, genes affecting oleic acid content in meat have been studied mainly to lower the fat melting point and improve tenderness;however, there has been no direct correlation demonstrated between beef taste and oleic acid. To investigate genes affecting other fatty acids other than oleic acid, polymorphisms of the fatty acid desaturase 2 (FADS2) gene were genotyped and associations with fatty acid profile in JBK beef were investigated. Amplifications of 5’-flanking regions, 12 exons, and 3’-untranslated regions of the FADS2 gene in three Japanese and five Western cattle breeds via PCR, were amplified, sequenced and SNPs were identified using specific TaqMan genotyping assay. Fatty acid composition of intramuscular adipose tissue of the Trapezius muscle was analyzed in JBK steers. Six of the 15 identified SNPs are novel and have never been registered in any public bovine SNP database. A non-synonymous SNP (rs211580559;C > T;294 Ala > Val) in exon 7 was examined in order to evaluate its association with fatty acid profiles. The data showed that highly significant association existed between rs211580559 and C18:2 (n-6) composition, and accounted for 22.3% of the variation. There were no significant relationships between rs2115-80559 and the other fatty acids. It was concluded that rs211580559 of the FADS2 gene may be a useful selection marker for reducing unfavorable volatiles generated from linoleic acid in JBK beef during the cooking process.
基金supported by the National Natural Science Foundation of China (81200973)the National Basic Research Development Program of China (2011CBA00400)an Independent Scientific Research Project of Fudan University (20520133484)
文摘Our previous studies have demonstrated that ceruloplasmin （CP） dysmetabolism is correlated with Parkinson＇s disease （PD）. However, the causes of decreased serum CP levels in PD patients remain to be clarified. This study aimed to explore the potential association between genetic variants of the CP gene and PD. Clinical features, serum CP levels, and the CP gene （both promoter and coding regions） were analyzed in 60 PD patients and 50 controls. A luciferase reporter system was used to investigate the function of promoter single-nucleotide polymorphisms （SNPs）. High-density comparative genomic hybridization microarrays were also used to detect large-scale copy-number variations in CP and an additional 47 genes involved in PD and/or copper/ iron metabolism. The frequencies of eight SNPs （one intronic SNP and seven promoter SNPs of the CP gene） and their haplotypes were significantly different between PD patients, especially those with lowered serum CP levels, and controls. However, the luciferase reporter system revealed no significant effect of the risk haplotype on promoter activity of the CP gene. Neither these SNPs nor their haplotypes were correlated with the Hoehn and Yahr staging of PD. The results of this study suggest that common genetic variants of CP are associated with PD and further investigation is needed to explore their functions in PD.
基金Beijing Science and Technology Innovation Fund(Grant No:KC2021-ZZ-0010-1)Shandong Provincial Natural Science Foundation Cancer Prevention Joint Fund(Grant No:ZR2022LZL004)Shanghai Cancer Prevention and Treatment Foundation(Grant No:CYBER-2022-003).
文摘Background: Identification of risk genes and loci associated with the recurrence and metastasis of breast cancer (BC) is ofutmost importance. Genome-wide association studies (GWASs) represent valuable tools for identifying the disease risk associated with a given single-nucleotide polymorphism (SNP);they offer significant insights into the disease progression mechanism by analyzing SNP information of the entire genome. Though GWAS has already identified several genetic susceptibilitySNPs for BC, their significance in the recurrence and metastasis of this cancer remains unclear. Here, we used a GWASapproach to identify SNPs specifically associated with the risk of BC recurrence and metastasis.Methods: This study adopted a two-stage GWAS approach. In the first stage, 97 pairs of BC patients with or without recurrenceand metastasis, treated at the Shandong Cancer Hospital and Institute from November 2013 to April 2014, were identified usingpropensity score matching. DNA extracted from the patient peripheral blood was then subjected to Illumina ASA chip analysisfor genome-wide SNP detection. In the second stage, the findings were verified in a validation set of 854 BC patients recruited atthe same hospital from May 2014 to June 2015. SNP genotyping was performed using time-of-flight mass spectrometry. The SNPloci and their corresponding genes and pathways were analyzed using the DAVID (https://david.ncifcrf.gov/) online enrichment analysis tool.Results: Based on the GWAS results, 191 SNP-related genes significantly associated with BC recurrence and metastasis wereidentified as expression quantitivative trait loci (p < 0.001). Functional and pathway enrichment analyses subsequently revealedthe potential involvement of glutamatergic synaptic transmission, calcium signaling, and insulin secretion pathways in BCrecurrence and metastasis. Based on genotype correlation and database expression levels, rs10108514, rs12920540, rs4273077,and rs4730155 were found to be significantly associated with the risk of BC recurrence and metastasis.Conclusion: Our study suggests that the SNPs rs10108514, rs12920540, rs4273077, and rs4730155 are correlated with the risk ofBC recurrence and metastasis, potentially by being implicated in glutamatergic synaptic transmission, calcium signaling, andinsulin secretion pathways.
基金supported by the National Natural Science Foundation of China,No.81070913(to ZYH)
文摘Two common polymorphisms of the peroxisome proliferator-activated receptor gamma(PPARG) gene, rs1801282 and rs3856806, may be important candidate gene loci affecting the susceptibility to ischemic stroke. This case-control study sought to identify the relationship between these two single-nucleotide polymorphisms and ischemic stroke risk in a northern Chinese Han population. A total of 910 ischemic stroke participants were recruited from the First Hospital of China Medical University, Shenyang, China as a case group, of whom 895 completed the study. The 883 healthy controls were recruited from the Health Check Center of the First Hospital of China Medical University, Shenyang, China. All participants or family members provided informed consent. The study protocol was approved by the Ethics Committee of the First Hospital of China Medical University, China on February 20, 2012(approval No. 2012-38-1). The protocol was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR-COC-17013559). Plasma genomic DNA was extracted from all participants and analyzed for rs1801282 and rs3856806 single nucleotide polymorphisms using a SNaPshot Multiplex sequencing assay. Odds ratios(ORs) and 95% confidence intervals(CIs) were calculated using unconditional logistic regression to estimate the association between ischemic stroke and a particular genotype. Results demonstrated that the G allele frequency of the PPARG gene rs1801282 locus was significantly higher in the case group than in the control group(P < 0.001). Individuals carrying the G allele had a 1.844 fold increased risk of ischemic stroke(OR = 1.844, 95% CI: 1.286–2.645, P < 0.001). Individuals carrying the rs3856806 T allele had a 1.366 fold increased risk of ischemic stroke(OR = 1.366, 95% CI: 1.077–1.733, P = 0.010). The distribution frequencies of the PPARG gene haplotypes rs1801282-rs3856806 in the control and case groups were determined. The frequency of distribution in the G-T haplotype case group was significantly higher than that in the control group. The risk of ischemic stroke increased to 2.953 times in individuals carrying the G-T haplotype(OR = 2.953, 95% CI: 2.082–4.190, P < 0.001). The rs1801282 G allele and rs3856806 T allele had a multiplicative interaction(OR = 3.404, 95% CI: 1.631–7.102, P < 0.001) and additive interaction(RERI = 41.705, 95% CI: 14.586–68.824, AP = 0.860;95% CI: 0.779–0.940;S = 8.170, 95% CI: 3.772–17.697) on ischemic stroke risk, showing a synergistic effect. Of all ischemic stroke cases, 86% were attributed to the interaction of the G allele of rs1801282 and the T allele of rs3856806. The effect of the PPARG rs1801282 G allele on ischemic stroke risk was enhanced in the presence of the rs3856806 T allele(OR = 8.001 vs. 1.844). The effect of the rs3856806 T allele on ischemic stroke risk was also enhanced in the presence of the rs1801282 G allele(OR = 2.546 vs. 1.366). Our results confirmed that the G allele of the PPARG gene rs1801282 locus and the T allele of the rs3856806 locus may be independent risk factors for ischemic stroke in the Han population of northern China, with a synergistic effect between the two alleles.
基金Supported by The Nationgal Natural Science Foundation of China,No.30571924
文摘AIM: To explore the associations of polymorphisms of lipopolysaccharide binding protein (LBP), cluster of differentiation 14 (CD14), toll-like receptor 4 (TLR-4), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) with the colorectal carcinoma (CRC) risk in Han Chinese. METHODS: Polymorphisms of LBP (rs1739654, rs223 2596, rs2232618), CD14 (rs77083413, rs4914), TLR-4 (rs5030719), IL-6 (rs13306435) and TNF-α (rs35131721) were genotyped in 479 cases of sporadic colorectal carcinoma and 486 healthy controls of Han Chinese in a case-control study. Single-nucleotide polymorphisms (SNPs) between cases and controls were analyzed by unconditional logistic regression. RESULTS: GA and GG genotypes of LBP rs2232596 were associated with a significantly increased risk ofCRC [odds ratio (OR) = 1.51, 95% confidence interval (CI) 1.15-1.99, P = 0.003; OR = 2.49, 95% CI 1.16-5.38, P = 0.016, respectively]. A similar association was also observed for the CG genotype of CD14 rs4914 (OR= 1.69, 95% CI 1.20-2.36, P = 0.002). In addition, a combination of polymorphisms in LBP rs2232596 and CD14 rs4914 led to a 3.4-fold increased risk of CRC (OR = 3.44, 95% CI 1.94-6.10, P = 0.000). CONCLUSION: This study highlights the LBP rs2232596 and CD14 rs4914 polymorphisms as biomarkers for elevated CRC susceptibility in the Chinese Han population.
基金supported by the National Natural Science Foundation of China,No.81472162(to MKZ)
文摘Single-nucleotide polymorphisms in the brain-derived neurotrophic factor gene may affect the secretion and function of brain-derived neurotrophic factor, thereby affecting the occurrence, severity and prognosis of ischemic stroke. This case-control study included 778 patients (475 males and 303 females, mean age of 64.0 ± 12.6 years) in the acute phase of ischemic stroke and 865 control subjects (438 males and 427 females, mean age of 51.7 ± 14.7 years) from the Department of Neurology, Wes: China Hospital, Sichuan University, China between September 2011 and December 2014. The patients' severities of neurological defici:s in the acute phase were assessed using the National Institutes of Health Stroke Scale immediately after admission to hospital. The ischemic stroke patients were divided into different subtypes according to the Trial of Org 10172 in Acute Stroke Treatment classification. Early prognosis was evaluated using the Modified Rankin Scale when the patients were discharged. Genomic DNA was extracted from peripheral blood of participants. Genotyping of rs7124442 and rs6265 was performed using Kompetitive Allele Specific polymerase chain reaction genotyping technology. Our results demonstrated that patients who carried the C allele of the rs7124442 locus had a lower risk of poor prognosis than the T allele carriers (odds ratio [OR]= 0.67;95% confidence interval [CI]: 0.45-1.00;P = 0.048). The patients with the CC or TC genotype also exhibited lower risk than TT carriers (OR = 0.65;95% CI: 0.42-1.00;P = 0.049). The AA genotype at the rs6265 locus was associated with the occurrence of ischemic stroke in patients with large-artery atherosclerosis (OR = 0.5& 95% CI: 0.37-0.90;P = 0.015). We found that the C allele (CC and TC genotypes) at the rs7124442 locus may be protective for the prognosis of ischemic stroke. The AA genotype at the rs6265 locus is likely a protective factor against the occurrence of ischemic stroke in patients with large-artery atherosclerosis. The study protocol was approved by the Ethics Committee of West China Hospital of Sichuan University, China (approval ID number 2008,4]) on July 25, 2008.
基金results in part from collaboration and network activities promoted under the frame of the international network GENIEUR (Genes in Irritable Bowel Syndrome Research Network Europe),which has been funded by the COST program (BM1106, www.GENIEUR.eu)currently supported by the European Society of Neurogastroenterology and Motility (ESNM, www.ESNM.eu)
文摘BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bowel syndrome(IBS).AIM To assess the association of HTR3 polymorphisms with depressive,anxiety,and somatization symptoms in individuals with IBS.METHODS In this retrospective study,623 participants with IBS were recruited from five specialty centers in Germany,Sweden,the United States,the United Kingdom,and Ireland.Depressive,anxiety,and somatization symptoms and sociodemographic characteristics were collected.Four functional SNPs—HTR3A c.-42C>T,HTR3B c.386A>C,HTR3C c.489C>A,and HTR3E c.*76G>A—were genotyped and analyzed using the dominant and recessive models.We also performed separate analyses for sex and IBS subtypes.SNP scores were calculated as the number of minor alleles of the SNPs above.The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays.RESULTS Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model(F_(depressive)=7.475,P_(depressive)=0.006;F_(anxiety)=6.535,P_(anxiety)=0.011).A higher SNP score(range 0-6)was linked to a worsened depressive symptoms score(F=7.710,P-linear trend=0.006)in IBS.The potential relevance of the HTR3C SNP was corroborated,showing changes in the expression level of 5-HT3AC variant receptors.CONCLUSION We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS.The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.
基金supported by funding from the CAMS Innovation Fund for Medical Sciences(CIFMS)[2016-I2M-1-002]National Basic Research Program of China [2010CB732601]+1 种基金National High Technology Research and Development Program of China [2015AA020407]National Natural Science Foundation of China [81470380]
文摘Objective The aim of this study is to establish whether cyclin-dependent kinase inhibitor 2B antisense RNA 1(CDKN2 B-AS1) gene polymorphisms are associated with premature triple-vessel disease(PTVD). Methods Nine single-nucleotide polymorphisms(rs1063192, rs10757274, rs1333042, rs1333049, rs2285327, rs3217986, rs3217992, rs4977574, and rs9632884) were genotyped in 884 PTVD patients and 907 control subjects(males ≤ 50 years old and females ≤ 60 years old) using the improved multiplex ligase detection reaction method. Results The allele frequencies of rs10757274 G, rs1333049 C, rs4977574 G(all P < 0.001), and rs3217986 G(P = 0.040) were significantly higher in the PTVD group than in the control group, but those of rs1063192 A, rs1333042 G, and rs9632884 C(all P < 0.001) were significantly lower in the former than in the latter. Logistic regression analysis revealed that homozygote AA of rs1333042 is associated with decreased risk for PTVD(OR = 0.42, 95% CI: 0.22-0.82, P = 0.011). In addition, the allele frequencies observed differed between genders. The G allele of rs3217986 was associated with increased risk for PTVD in male patients only(OR = 2.94, 95% CI: 1.27-6.80, P = 0.012) in the dominant model, and no positively mutated allele was found in female patients. Conclusion Polymorphisms of the CDKN2 B-AS1 gene are associated with the incidence of PTVD in the Chinese population. Furthermore, the frequencies of mutated alleles differed between genders.
基金Supported by Lithuanian Research Council Grant,No.MIP-14418
文摘AIM To evaluate associations between mi RNA target genes IL12B,INSR,CCND1 and IL10 polymorphisms and gastric cancer(GC)in European population.METHODS Gene polymorphisms were analyzed in 508 controls and474 GC patients from 3 tertiary centers in Germany,Lithuania and Latvia.Controls were patients from the out-patient departments,who were referred for upper endoscopy because of dyspeptic symptoms and had no history of previous malignancy.Gastric cancer(GC)patients had histopathological verification of gastric adenocarcinoma.Genomic DNA was extracted using salting out method from peripheral blood mononuclear cells.IL12B T>G(rs1368439),INSR T>C(rs1051690),CCND1 A>C(rs7177)and IL10 T>C(rs3024498)SNPs were genotyped by the real-time polymerase chain reaction.Associations between gene polymorphism and GC were evaluated using multiple logistic regression analysis with adjustment for sex,age and country of birth.RESULTS We observed similar distribution of genotypes and allelic frequencies of all polymorphisms between GC patients and controls except of INSR rs1051690.The frequency of the T allele of INSR gene was significantly higher in GC patients than in controls(23.26%and 19.19%respectively,P=0.028).CT genotype was also more prevalent in patients compared to control group(38.48%and 30.12%respectively,P<0.021).Logistic regression analysis revealed that only one polymorphism(rs1051690 in INSR gene)was associated with increased risk of GC.Carriers of CT genotype had higher odds of GC when compared to CC genotype(OR=1.45,95%PI:1.08-1.95,P=0.01).Similar association was observed in a dominant model for INSR gene,where comparison of TT+CT vs CC genotypes showed an increased risk of GC(OR=1.44,95%PI:1.08-1.90,P=0.01).Other analyzed SNPs were not associated with the presence of GC.CONCLUSION INSR rs1051690 SNP is associated with increased risk of GC,while polymorphisms in IL12B,CCND1 and IL10genes are not linked with the presence of GC.
基金Acknowledgment This work was supported by the National Natural Science Foundation of China （No. 30470960）, and the National Basic Research Program of China （No. 2004CB518805）. The authors declare that there is no conflict of interest that would prejudice the impartiality of this scientific work.
文摘TSSK6 is a member of the testis-specific serine/threonine kinase family. Male Tssk6 knockout mice are infertile owing to sperrnatogenic impairment,including sperm count reduction,a decrease in motile sperm number and motility rates,and an increase in the number of sperms with abnormal morphology. We investigated the possible association between variations oftbe TSSK6 gene and spermatogenic impairment in humans. Mutation screening of TSSK6 was carried out in 519 patients with azoospermia （n = 273） or severe oligozoospermia （n = 246） and in 359 controls with normozoospermia by denaturing high-performance liquid chromatography and DNA sequencing. The frequencies of alleles and genotypes of gene polymorphism were compared between patients and controls. A novel triallelic polymorphism in TSSK6,c.822＋126T〉G/C,was identified. The frequencies of genotype TT and allele T were increased dramatically in infertile patients compared with controls,whereas genotype TG,allele G and allele C frequencies were significantly higher in controls than in patients. Further study revealed that the allele C frequency of controls was remarkably higher than that of patients with oligospermia. Our findings,for the first time,suggested an association of c.822＋I26T〉G/C in TSSK6 with spermatogenic impairment in humans in which allele T may be a risk factor for male infertility,while alleles C and G may decrease susceptibility to male infertility.
文摘Objective To investigate the association between two polymorphisms of follicle stimulating hormone receptor （FSHR） gene and polycystic ovary syndrome （PCOS） susceptibility. Methods Case-control studies on relationship of Thr307Ala and Asn680Ser polymorphisms in FSHR gene and PCOS susceptibility were searched from PubMed, ISI web of knowledge, EBSCO, and China National Knowledge Infrastructure （CNKI） databases up to March 21, 2013. The pooled odds ratio （OR） and 95% confidence interval （CO were calculated using fixed- or random-effect model based on heterogeneity test in 5 genotype models analyses. Results A total of 11 studies were included in the Meta-analysis. The random-effect analysis showed Asn680Ser was significantly associated with the reduced susceptibility to PCOS with dominant model （Asn/Asn＋Asn/Ser vs. Ser/Ser, OR=0.83, 95% CI： 0.69-1.00）, recessive model （Asn/Asn vs. Asn/Ser＋ Ser/Ser, OR=0.84, 95% CI： 0.72-0.98）, homozygote comparison （Ash/Ash vs. Ser/Ser, 0R=0.79, 95% CI： 0.63-0.98）, and the allele contrast （Asn vs. Ser, OR=0.87, 95% CI： 0.79-0.97） respectively（P=0.02, I2=56.0%）, being protective factors for PCOS. However, no significant associations were found between Thr307Ala and PCOS. Conclusion There might be a significant association between Asn680Ser polymorphism and PCOS.
基金supported by the National Natural Science Foundation of China,No.81271321(to HYZ)a grant from the Department of Science and Technology Research Projects in Sichuan Province of China,No.2013FZ0015(to HYZ)the Fundamental Research Funds for the Central Universities,China,No.2017SCU11049(to QZ)
文摘Variants at the GTF2I repeat domain containing 1(GTF2IRD1)–GTF2I locus are associated with primary Sj?gren's syndrome, systemic lupus erythematosus, and rheumatoid arthritis. Numerous studies have indicated that this susceptibility locus is shared by multiple autoimmune diseases. However, until now there were no studies of the correlation between GTF2IRD1–GTF2I polymorphisms and neuromyelitis optica spectrum disorders(NMOSD). This case control study assessed this association by recruiting 305 participants with neuromyelitis optica spectrum disorders and 487 healthy controls at the Department of Neurology, from September 2014 to April 2017. Peripheral blood was collected, DNA extracteds and the genetic association between GTF2IRD1–GTF2I polymorphisms and neuromyelitis optica spectrum disorders in the Chinese Han population was analyzed by genotyping. We found that the T allele of rs117026326 was associated with an increased risk of neuromyelitis optica spectrum disorders(odds ratio(OR) = 1.364, 95% confidence interval(CI) 1.019–1.828; P = 0.037). This association persisted after stratification analysis for aquaporin-4 immunoglobulin G antibodies(AQP4-IgG) positivity(OR = 1.397, 95% CI 1.021–1.912; P = 0.036) and stratification according to coexisting autoimmune diseases(OR = 1.446, 95% CI 1.072–1.952; P = 0.015). Furthermore, the CC genotype of rs73366469 was frequent in AQP4-IgG-seropositive patients(OR = 3.15, 95% CI 1.183–8.393, P = 0.022). In conclusion, the T allele of rs117026326 was associated with susceptibility to neuromyelitis optica spectrum disorders, and the CC genotype of rs73366469 conferred susceptibility to AQP4-IgG-seropositivity in Han Chinese patients. The protocol was approved by the Ethics Committee of West China Hospital of Sichuan University, China(approval number: 2016-31) on March 2, 2016.
文摘Objective: To investigate the association between TLR3 and TLR7 polymorphisms with susceptibility and clinical manifestations of Chikungunya Fever.Methods: A total of 177 individuals were studied: 73 patients with a confirmed diagnosis for Chikungunya virus and 104 non-infected individuals. Polymorphisms were determined by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism(PCR-RFLP).Results: Our analysis showed an increased CC genotype frequency of the TLR7 rs3853839 polymorphism in male patients compared to control(29% versus 2%,respectively; OR=20.69; 95% CI=2.55-167.36; P<0.001). Furthermore,arthritis(acute and chronic) was frequently found in CC male patients. On the contrary,65% of CG carriers were no-infected males(29% versus 65%,respectively; OR=0.23,95% CI=0.48-3.04; P=0.002). Finally,we observed a higher frequency of lymphopenia in CG male patients(CG=666.86±233.77,GG=1,314.27±752.29 cells/mm3,P=0.047). Conclusions: Our results suggest the TLR7 rs3853839 polymorphism is associated with lymphopenia and increased susceptibility to Chikungunya Fever in males.
基金Supported by Sao Paulo Research Foundation(FAPESP),No.2011/23969-1 and No.2012/02473-0Coordination for the Improvement of Higher Education Personnel(CAPES)(Master grant)and National Council of Technological and Scientific Development(CNPq),No.310582/2014-8
文摘AIM To investigate the contribution of polymorphisms in the CYP1A1, CYP2E1 and EPHX1 genes on sporadic colorectal cancer(SCRC) risk. METHODS Six hundred forty-one individuals(227 patients with SCRC and 400 controls) were enrolled in the study. The variables analyzed were age, gender, tobacco and alcohol consumption, and clinical and histopathological tumor parameters. The CYP1A1 *2A, CYP1A1 *2C CYP2E1 *5B and CYP2E1 *6 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). The EPHX1 Tyr113 His, EPHX1 His139 Arg and CYP1A1 *2C polymorphisms were detected by real-time PCR. Chisquared test and binary logistic regression were used in the statistical analysis. Haplotype analysis was conducted using the Haploview program, version 2.05.RESULTS Age over 6 2 years was a risk factor for SCRC development(OR = 7.54, 95%CI: 4.94-11.50, P < 0.01). Male individuals were less susceptible to SCRC(OR = 0.55, 95%CI: 0.35-0.85, P < 0.01). The CYP2E1*5B polymorphism was associated with SCRC in the codominant(heterozygous genotype: OR = 2.66, 95%CI: 1.64-4.32, P < 0.01), dominant(OR = 2.82, 95%CI: 1.74-4.55, P < 0.01), overdominant(OR = 2.58, 95%CI: 1.59-4.19, P < 0.01), and log-additive models(OR = 2.84, 95%CI: 1.78-4.52, P < 0.01). The CYP2E1*6 polymorphism was associated with an increased SCRC risk in codominant(heterozygous genotype: OR = 2.81, 95%CI: 1.84-4.28, P < 0.01; homozygous polymorphic : OR = 7. 3 2, 9 5 % C I : 1.85-28.96, P < 0.01), dominant(OR = 2.97, 95%CI: 1.97-4.50, P < 0.01), recessive(OR = 5.26, 95%CI: 1.35-20.50, P = 0.016), overdominant(OR = 2.64, 95%CI: 1.74-4.01, P < 0.01), and log-additive models(OR = 2.78, 95%CI: 1.91-4.06, P < 0.01). The haplotype formed by the minor alleles of the CYP2E1*5B(C) and CYP2E1*6(A) polymorphisms was associated with SCRC(P = 0.002). However, the CYP1A1 *2A, CYP1A1 *2C, EPHX1 Tyr113 His and EPHX1 His139 Arg polymorphisms were not associated with SCRC.CONCLUSION In conclusion, the results demonstrated that CYP2E1*5B and CYP2E1*6 minor alleles play a role in the development of SCRC.
基金Projcct supported by the National Natural Science Foundation of China （No. 81072315）
文摘Objective： A study in a Caucasian population has identified two single-nucleotide polymorphisms （SNPs） in ZNF533, one in DOCK4, and two in IMMP2L, which were all significantly associated with autism. They are located in AUTS1 and AUTS5, which have been identified as autism susceptibility loci in several genome-wide screens. The present study aimed to investigate whether ZNF533, DOCK4, and IMMP2L genes are also associated with autism in a northeastern Chinese Han population. Methods： We performed a similar association study using families with three individuals （one autistic child and two unaffected parents）. A family-based transmission disequilibrium test （TDT） was used to analyze the results. Results： There were significant associations between autism and the two SNPs of ZNF533 gene （rs11885327： X^2=4.5200, P=0.0335; rs1964081 ：）（2=4.2610, P=0.0390） and the SNP of DOCK4 gene （rs2217262 X^2=5.3430, P=0.0208）. Conclusions： Our data suggest that ZNF533 and DOCK4 genes are linked to a predisposition to autism in the northeastern Chinese Han population.
