The KCNQ family of genes(KCNQ1–KCNQ5),encoding voltage-gated K+(Kv)channels,have been demonstrated to play potential pathophysiological roles in cancers.However,the associations between genetic variants located in KC...The KCNQ family of genes(KCNQ1–KCNQ5),encoding voltage-gated K+(Kv)channels,have been demonstrated to play potential pathophysiological roles in cancers.However,the associations between genetic variants located in KCNQ family genes and gastric cancer survival remain unclear.In this study,a large-scale cohort comprising 1135 Chinese gastric cancer patients was enrolled to identify genetic variants in KCNQ family genes associated with overall survival(OS).Based on the survival evaluation of all five KCNQ family genes,KCNQ1 was selected for subsequent genetic analysis.In both Cox regression model and stepwise Cox regression model used to evaluate survival-related genetic variants,we found that KCNQ1 rs10832417G>T was associated with an increased OS in gastric cancer patients(adjusted hazards ratio[HR]=0.84,95%confidence interval[CI]:0.72–0.98,P=0.023).Subsequently,a nomogram was constructed to enhance the prognostic capacity and clinical translation of rs10832417 variants.The rs10832417 T allele was predicted to increase the minimum free energy of the secondary structure.Furthermore,we observed that gastric cancer patients with downregulated KCNQ1expression had a poorer survival across multiple public datasets.The findings of the present study indicate that KCNQ1 rs10832417 may serve as an independent prognostic predictor of gastric cancer,providing novel insights into the progression and survival of the disease.展开更多
Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1(C1GALT1)is known to play a critical role in the development of gastric cancer,but few studies have elucidated associations between geneti...Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1(C1GALT1)is known to play a critical role in the development of gastric cancer,but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer risk.By using the genome-wide association study data from the database of Genotype and Phenotype(dbGAP),we evaluated such associations with a multivariable logistic regression model and identified that the rs35999583 G>C in C1GALT1 was associated with gastric cancer risk(odds ratio,0.83;95% confidence interval[CI],0.75-0.92;P=3.95×10^(-4)).C1GALT1 mRNA expression levels were significantly higher in gastric tumor tissues than in normal tissues,and gastric cancer patients with higher C1GALT1 mRNA levels had worse overall survival rates(hazards ratio,1.33;95%CI,1.05-1.68;P_(log-rank)=1.90×10^(-2)).Furthermore,we found that C1GALT1 copy number differed in various immune cells and that C1GALT1 mRNA expression levels were positively correlated with the infiltrating levels of CD4^(+)T cells and macrophages.These results suggest that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 into a promising predictor of gastric cancer susceptibility and immune status.展开更多
Inflammatory bowel diseases (IBD) are complex multifactorial disorders that include Crohn’s disease (CD) and ulcerative colitis (UC). Considering that IBD is a genetic and multifactorial disease, we screened for the ...Inflammatory bowel diseases (IBD) are complex multifactorial disorders that include Crohn’s disease (CD) and ulcerative colitis (UC). Considering that IBD is a genetic and multifactorial disease, we screened for the distribution dynamism of IBD pathogenic genetic variants (single nucleotide polymorphisms;SNPs) and risk factors in four (4) IBD pediatric patients, by integrating both clinical exome sequencing and computational statistical approaches, aiming to categorize IBD patients in CD and UC phenotype. To this end, we first aligned genomic read sequences of these IBD patients to hg19 human genome by using bowtie 2 package. Next, we performed genetic variant calling analysis in terms of single nucleotide polymorphism (SNP) for genes covered by at least 20 read genomic sequences. Finally, we checked for biological and genomic functions of genes exhibiting statistically significant genetic variant (SNPs) by introducing Fitcon genomic parameter. Findings showed Fitcon parameter as normalizing IBD patient’s population variability, as well as inducing a relative good clustering between IBD patients in terms of CD and UC phenotypes. Genomic analysis revealed a random distribution of risk factors and as well pathogenic SNPs genetic variants in the four IBD patient’s genome, claiming to be involved in: i) Metabolic disorders, ii) Autoimmune deficiencies;iii) Crohn’s disease pathways. Integration of genomic and computational statistical analysis supported a relative genetic variability regarding IBD patient population by processing IBD pathogenic SNP genetic variants as opposite to IBD risk factor variants. Interestingly, findings clearly allowed categorizing IBD patients in CD and UC phenotypes by applying Fitcon parameter in selecting IBD pathogenic genetic variants. Considering as a whole, the study suggested the efficiency of integrating clinical exome sequencing and computational statistical tools as a right approach in discriminating IBD phenotypes as well as improving inflammatory bowel disease (IBD) molecular diagnostic process.展开更多
The present study was designed to examine the contributions of the fatty acid elongase （ELOVL） gene polymorphisms to the levels of polyunsaturated fatty acids （PUFAs） in breast milk. Two hundred and nine healthy H...The present study was designed to examine the contributions of the fatty acid elongase （ELOVL） gene polymorphisms to the levels of polyunsaturated fatty acids （PUFAs） in breast milk. Two hundred and nine healthy Han Chinese mothers were included in the study. Carriers of minor alleles of SNPs （rs2397142 and rs9357760） in ELOVL5 were associated with higher levels of linoleic acid （LA）, dihomo-γ-linolenic acid （DGLA）, arachidonic acid （AA）, docosatetraenoic acid （DTA）, docosahexenoic acid （DHA）, while in rs209512 of ELOVL5 the carriers of minor alleles had lower levels of DTA compared to major homozygote alleles （P ranged from 0.004-0.046）, and genetically explained variability ranged from 3.2% for eicosapentaenoic acid （EPA） to 6.0% for LA. Our findings demonstrated that common variation in ELOVL5 gene encoding rate-limiting enzymes in the metabolism of PUFAs contribute to the PUFAs in breast milk.展开更多
People living on the high plateaus of the world have long fascinated biological anthropologists and geneticists because they live in ＂thin air＂ and epitomize an extreme of human biological adaptation.
Infection is the leading cause of complication after liver transplantation, causing morbidity and mortality in the first months after surgery. Allograft rejection is mediated through adaptive immunological responses, ...Infection is the leading cause of complication after liver transplantation, causing morbidity and mortality in the first months after surgery. Allograft rejection is mediated through adaptive immunological responses, and thus immunosuppressive therapy is necessary after transplantation. In this setting, the presence of genetic variants of innate immunity receptors may increase the risk of post-transplant infection, in comparison with patients carrying wild-type alleles. Numerous studies have investigated the role of genetic variants of innate immune receptors and the risk of complication after liver transplantation, but their results are discordant. Tolllike receptors and mannose-binding lectin are arguably the most important studied molecules; however, many other receptors could increase the risk of infection after transplantation. In this article, we review the published studies analyzing the impact of genetic variants in the innate immune system on the development of infectious complications after liver transplantation.展开更多
Genetic variants in glioma tumor suppressor candidate region gene 1 （GLTSCR1） and ATM serine/threonine kinase （ATM） have been associated with various cancer risks. Epidemiological studies also revealed the associa...Genetic variants in glioma tumor suppressor candidate region gene 1 （GLTSCR1） and ATM serine/threonine kinase （ATM） have been associated with various cancer risks. Epidemiological studies also revealed the association of variants of GLTSCR1 and ATM genes with different brain tumors. However, little is known about the relationship between both gene polymorphisms and lung cancer risk. We conducted a Chinese hospital-based casecontrol study involving 384 lung cancer cases and 387 cancer-free controls. No significant differences in the single polymorphism （GLTSCR1 rs1035938 and ATM rs11212592） association were found in five genetic models （co-dominant, dominant, recessive, overdominant and log-additive models） （adjusted by smoking duration）. Join effect of three SNPs （PPPIR13L rs1970764, CD3EAP rs967591, GLTSCR1 rs1035938） on chromosome 19q 13.3 showed that the designated haplotype2 （rs 1970764 G-rs967591 A-rs 1035938 C） [OR （95% CI）=1.60 （1.11-2.32）, P=0.012] and haplotype8 （rs 1970764 G-rs967591 G-rs 1035938 T） [OR （95% CI）=2.45 （1.17-5.12）, P=0.018] were associated with increased risk of lung cancer （adjusted by smoking duration）. The analysis ofmultifactor dimensionality reduction revealed that two 3-way models were the best fit models in analyses of 2 loci （P〈0.001） or 4 loci （P=0.015-0.016）. The entropy-based analysis indicated the strongest synergistic effect between PPPIR13L rs1970764 and ATM rs11212592 in analysis of four genes. In conclusion, our study suggests that haplotypes consisting of PPPIR13L rs1970764- CD3EAP rs967591-GLTSCR1 rs1035938 on Chr19q13.3, interaction of smoking and GLTSCR1 rs1035938-ATM rs11212592, and synergistic action of PPPIR13L rs1970764 and ATM rs 11212592 may associate with lung cancer risk in the Chinese population.展开更多
Background Pan-genomics is a recently emerging strategy that can be utilized to provide a more comprehensive characterization of genetic variation.Joint calling is routinely used to combine identified variants across ...Background Pan-genomics is a recently emerging strategy that can be utilized to provide a more comprehensive characterization of genetic variation.Joint calling is routinely used to combine identified variants across multiple related samples.However,the improvement of variants identification using the mutual support information from mul-tiple samples remains quite limited for population-scale genotyping.Results In this study,we developed a computational framework for joint calling genetic variants from 5,061 sheep by incorporating the sequencing error and optimizing mutual support information from multiple samples’data.The variants were accurately identified from multiple samples by using four steps:(1)Probabilities of variants from two widely used algorithms,GATK and Freebayes,were calculated by Poisson model incorporating base sequencing error potential;(2)The variants with high mapping quality or consistently identified from at least two samples by GATK and Freebayes were used to construct the raw high-confidence identification(rHID)variants database;(3)The high confidence variants identified in single sample were ordered by probability value and controlled by false discovery rate(FDR)using rHID database;(4)To avoid the elimination of potentially true variants from rHID database,the vari-ants that failed FDR were reexamined to rescued potential true variants and ensured high accurate identification variants.The results indicated that the percent of concordant SNPs and Indels from Freebayes and GATK after our new method were significantly improved 12%-32%compared with raw variants and advantageously found low frequency variants of individual sheep involved several traits including nipples number(GPC5),scrapie pathology(PAPSS2),sea-sonal reproduction and litter size(GRM1),coat color(RAB27A),and lentivirus susceptibility(TMEM154).Conclusion The new method used the computational strategy to reduce the number of false positives,and simulta-neously improve the identification of genetic variants.This strategy did not incur any extra cost by using any addi-tional samples or sequencing data information and advantageously identified rare variants which can be important for practical applications of animal breeding.展开更多
Endometriosis is defined as the presence of endometrium-like tissue outside the uterus,80%of which occur in the ovaries.It is characterized by an estrogen-dependent produces periodic and repeated bleeding,and may be a...Endometriosis is defined as the presence of endometrium-like tissue outside the uterus,80%of which occur in the ovaries.It is characterized by an estrogen-dependent produces periodic and repeated bleeding,and may be accompanied by clinical symptoms such as dysmenorrhea,fatigue,dysuria,deep dyspareunia,and infertility.Due to the complex etiology and the yet-unknown pathogenesis of endometriosis,and the treatment effect is not ideal,causing significant physical and mental harm to reproductive-age women;thus,it has become a hot research topic.Endometriosis is still a mysterious disease of unknown origin and pathogenesis.Genetic factors are known to affect the manifestation and progression of endometriosis.A selection of genetic studies revealed genetic mutations and polymorphisms of endometriosis and their effects on the risk of developing this disease.This paper aimed to discuss the genetic variants associated with the risk of endometriosis and provided information to enrich the gene spectrum of endometriosis.展开更多
Objective：Recent evidence indicates that dysregulation of microRNA （miRNA） biogenesis is implicated in cancer development and progression.Based on the important role of miRNA biogenesis genes in carcinogenesis,we h...Objective：Recent evidence indicates that dysregulation of microRNA （miRNA） biogenesis is implicated in cancer development and progression.Based on the important role of miRNA biogenesis genes in carcinogenesis,we hypothesized that genetic variations of the miRNA biogenesis genes may modulate susceptibility to cervical cancer.Methods：We identified three single nucleotide polymorphisms （SNPs） located in the 3＇-untranslated regions （3＇-UTR） of of miRNA biogenesis key genes （rs1057035 in DICER,rs3803012 in RAN and rs10773771 in HIWI） and genotyped these SNPs in a case-control study of 1,486 cervical cancer cases and 1,549 cancer-free controls in Chinese women.Results：Logistic regression analyses showed that no significant associations were observed between the three SNPs and cervical cancer risk [rs3803012 in RAN AG/GG vs.AA adjusted OR =1.104,95 ％ confidence interval （CI）：0.859-1.419; rs1057035 in DICER CT/CC vs.TT adjusted OR =0.962,95％ CI：0.805-1.149;rs10773771 in HIWICT/CC vs.TT adjusted OR =0.963,95％ CI：0.826-1.122].Conclusions：The findings did not suggest that genetic variants in the 3＇-UTR of RAN,DICER and HIWI of miRNA biogenesis genes were associated with the risk of cervical cancer in this Chinese population.展开更多
Aberrant alternative polyadenylation(APA)events play an important role in cancers,but little is known about whether APA-related genetic variants contribute to the susceptibility to bladder cancer.Previous genome-wide ...Aberrant alternative polyadenylation(APA)events play an important role in cancers,but little is known about whether APA-related genetic variants contribute to the susceptibility to bladder cancer.Previous genome-wide association study performed APA quantitative trait loci(apaQTL)analyses in bladder cancer,and identified 17955 single nucleotide polymorphisms(SNPs).We found that gene symbols of APA affected by apaQTL-associated SNPs were closely correlated with cancer signaling pathways,high mutational burden,and immune infiltration.Association analysis showed that apaQTL-associated SNPs rs34402449 C>A,rs2683524 C>T,and rs11540872 C>G were significantly associated with susceptibility to bladder cancer(rs34402449:OR=1.355,95%confidence interval[CI]:1.159-1.583,P=1.33×10^(−4);rs2683524:OR=1.378,95%CI:1.164-1.632,P=2.03×10^(−4);rs11540872:OR=1.472,95%CI:1.193-1.815,P=3.06×10^(−4)).Cumulative effect analysis showed that the number of risk genotypes and smoking status were significantly associated with an increased risk of bladder cancer(P_(trend)=2.87×10^(−12)).We found that PRR13,being demonstrated the most significant effect on cell proliferation in bladder cancer cell lines,was more highly expressed in bladder cancer tissues than in adjacent normal tissues.Moreover,the rs2683524 T allele was correlated with shorter 3′untranslated regions of PRR13 and increased PRR13 expression levels.Collectively,our findings have provided informative apaQTL resources and insights into the regulatory mechanisms linking apaQTL-associated variants to bladder cancer risk.展开更多
Dear Editor,Multi-omics association analysis is a key method in crop germplasm research,helping to elucidate the regulatory mechanisms of agronomic traits(Liu et al.,2020;Liang et al.,2021).However,most existing multi...Dear Editor,Multi-omics association analysis is a key method in crop germplasm research,helping to elucidate the regulatory mechanisms of agronomic traits(Liu et al.,2020;Liang et al.,2021).However,most existing multi-omics association studies focus on omics data under a single condition,posing challenges in identifying stress-related agronomically important genes.This difficultymainly arises fromthe increased complexity ofmulti-omics analyseswhen comparing control and stress conditions.展开更多
Cerebral palsy(CP)refers to a spectrum of permanent movement disorders commonly accompanied by other neurodevelopmental disorders(NDDs).CP is the most common form of physical disability in children,with an estimated p...Cerebral palsy(CP)refers to a spectrum of permanent movement disorders commonly accompanied by other neurodevelopmental disorders(NDDs).CP is the most common form of physical disability in children,with an estimated prevalence of 2 to 3 per 1,000 live births worldwide,and the incidence of CP at term has not changed markedly in the past 50 years[1].The prevalence,severity,and burden of CP make it a high public health priority for prevention.Despite several reports of antenatal and perinatal risk factors for CP,determining the cause of CP remains challenging,as many children with CP have no known risk factors,and some children with risk factors do not develop CP[2].Theoretically,early interventions could improve neuroplasticity and functional outcomes,but early diagnosis of CP before a child’s first birthday requires later confirmation,which hinders early specific interventions.展开更多
Congenital scoliosis(CS)is a prevalent spinal deformity with a multifaceted etiology that remains incompletely understood.Recent advances in genetic and epigenetic research have provided novel insights into CS pathoge...Congenital scoliosis(CS)is a prevalent spinal deformity with a multifaceted etiology that remains incompletely understood.Recent advances in genetic and epigenetic research have provided novel insights into CS pathogenesis.Herein,we review the current progress in genetics and epigenetics to examine genetic variants,susceptibility factors,and the epigenetic regulatory mechanisms implicated in CS.Through an analysis of diverse genetic markers,chromosomal abnormalities,and epigenetic modifications,the correlation between genetic predisposition and environmental influences in CS pathogenesis is elucidated.By integrating these genetic and epigenetic findings,this study aims to clarify the underlying etiology of CS to provide guidance on future clinical interventions and promote the development of personalized therapeutic strategies.展开更多
BACKGROUND MicroRNAs play a key role in regulating gene expression in human cells.Singlenucleotide variants in these molecules have been linked to cancer development,particularly breast cancer(BrC).AIM To analyze the ...BACKGROUND MicroRNAs play a key role in regulating gene expression in human cells.Singlenucleotide variants in these molecules have been linked to cancer development,particularly breast cancer(BrC).AIM To analyze the association of three microRNA polymorphisms with the risk of BrC in women from western Mexico.METHODS This case-control study included 71 women diagnosed with BrC and 215 women without BrC.Genotypes were determined using a real-time polymerase chain reaction allelic discrimination assay.Multiple genetic models-dominant,recessive,over-dominant,additive,and multiple comparison-were applied to assess the risk.RESULTS The over-dominant model showed that the C/T genotype of MIR196A2(rs11614913)is a protective factor against the ductal histological subtype of BrC in women from western Mexico[odds ratio(OR)=0.4687,95%confidence interval(CI):0.2205-0.9963,P=0.0489].A protective effect was also observed for the C/A genotype(OR=0.2612,95%CI:0.0900-0.7582,P=0.0135)and A allele(OR=0.2826,95%CI:0.0993-0.8044,P=0.0179)of MIR618(rs2682818).No significant association was found between MIR200C(rs73262897)and BrC risk.CONCLUSION The C/T genotype of rs11614913 in MIR196A2,and C/A genotype and A allele of rs2682818 in MIR618,are associated with a protective effect against BrC in women from western Mexico.展开更多
Nonobstructive azoospermia(NOA),one of the most severe types of male infertility,etiology often remains unclear in most cases.Therefore,this study aimed to detect four biallelic detrimental variants(0.5%)in the minich...Nonobstructive azoospermia(NOA),one of the most severe types of male infertility,etiology often remains unclear in most cases.Therefore,this study aimed to detect four biallelic detrimental variants(0.5%)in the minichromosome maintenance domain containing 2(MCMDC2)genes in 768 NOA patients by whole-exome sequencing(WES).Hematoxylin and eosin(H&E)demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients(c.1360G>T,c.1956G>T,and c.685C>T)and hypospermatogenesis in one patient(c.94G>T),as further confirmed through immunofluorescence(IF)staining.The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis.The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses.The results revealed four MCMDC2 variants related to NOA,which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.展开更多
Objective： To compared the therapeutic effect of a Chinese patent medicine Naoxintong Capsule（脑心通胶囊, NXT） and aspirin with adjusted-dose warfarin in Chinese elderly patients（over 65 years） with nonvalvular a...Objective： To compared the therapeutic effect of a Chinese patent medicine Naoxintong Capsule（脑心通胶囊, NXT） and aspirin with adjusted-dose warfarin in Chinese elderly patients（over 65 years） with nonvalvular atrial fibrillation（NVAF） and genetic variants of vitamin K epoxide reductase（VKORC1）, who are at high-risk of thromboembolism. Methods： A total of 151 patients, with NVAF and AA genotype of VKORC1-1639（a sensitive genotype to warfarin） and a CHA2 DS2-VASc clinical risk score of 2 or above, were chosen for this study. Patients were randomized into two groups and orally treated with a combination of aspirin（100 mg/day） and NXT（1.6 g thrice a day） or adjusted-dose warfarin [international normalized ratio 2.0–3.0）. The primary end points including ischemic stroke and death as well as the secondary end points including hemorrhage events were followed up for at least 1 year. Results： Baseline clinical data and the rates of primary end points were similar between groups. However, the rate of serious bleeding（secondary event） in the combination therapy group was lower than that in the adjusted-dose warfarin group（0% vs. 7.9%, odds ratio： 0.921, 95% confidence interval： 0.862–0.984, P=0.028）. Conclusions： Aspirin combined with NXT and warfarin displayed comparable rates of primary end point including ischemic stroke and all-cause death during the 1-year follow-up. However, as compared with warfarin, the combination therapy reduced the rate of serious bleeding. Therefore, aspirin combined with NXT might provide an alternative pharmacotherapy in preventing ischemic stroke for elderly patients with NAVF who cannot tolerate warfarin.（No. ChiC TR-TRC-13003596）展开更多
The development of premature coronary artery disease(PCAD)is dependent on both genetic predisposition and traditional risk factors.Strategies for unraveling the genetic basis of PCAD have evolved with the advent of mo...The development of premature coronary artery disease(PCAD)is dependent on both genetic predisposition and traditional risk factors.Strategies for unraveling the genetic basis of PCAD have evolved with the advent of modern technologies.Genome-wide association studies(GWASs)have identified a considerable number of common genetic variants that are associated with PCAD.Most of these genetic variants are attributable to lipid and blood pressure-related single-nucleotide polymorphisms(SNPs).The genetic variants that predispose individuals to developing PCAD may depend on race and ethnicity.Some characteristic genetic variants have been identified in Chinese populations.Although translating this genetic knowledge into clinical applications is still challenging,these genetic variants can be used for CAD phenotype identification,genetic prediction and therapy.In this article we will provide a comprehensive review of genetic variants detected by GWASs that are predicted to contribute to the development of PCAD.We will highlight recent findings regarding CAD-related genetic variants in Chinese populations and discuss the potential clinical utility of genetic variants for preventing and managing PCAD.展开更多
This study was performed for investigation the relationship between variants of MTP gene polymorphism and the development of NAFLD in patients with and without MS.The study was included 174 NAFLD patients(106 with MS ...This study was performed for investigation the relationship between variants of MTP gene polymorphism and the development of NAFLD in patients with and without MS.The study was included 174 NAFLD patients(106 with MS and 68 without MS),and 141 healthy control subjects.The 493 G/T polymorphism of MTP gene was evaluated by PCR-RFLP method.The frequency of MTP TT genotype and T allele were significantly higher in NAFLD patients when compared to healthy controls.Moreover,a significant association in MTP gene polymorphism was observed in NAFLD patients with MS compared to NAFLD patients without MS and controls.Our study suggested that MTP 493 G/T gene polymorphism may act as susceptibility biomarker for NAFLD and MS.展开更多
Objective： To examine the association of genetic variants with characteristic symptoms of type 2 diabetes mellitus （T2DM）. Methods： A matched case-control study was performed to investigate the association between...Objective： To examine the association of genetic variants with characteristic symptoms of type 2 diabetes mellitus （T2DM）. Methods： A matched case-control study was performed to investigate the association between common variants in four genes （CDKAL1, GLIS3, GRK5, and TCFTL2） and symptoms of T2DM. Symptoms were examined with questionnaire for 710 subjects. Genomic DNA was extracted from peripheral blood mononuclear cell by salting-out procedure. Genotyping was carried out by direct sequencing of the unpurified polymerase chain reaction products. Result： Most of the T2DM patients pressented characteristic symptoms, such as feeling weak in limbs （P=0.0057）, hand tremor （P=0.0208）, bradymasesis （P=0.0234）, and polyuria （P=0.0051）. Some of the T2DM patients shared characteristic symptoms, such as desire for cold drinks （P=0.0304）, polyphagia （P=0.0051）, and furred tongue （P=0.028）. The impaired glucose regulation （IGR） cases took only one characteristic symptom of frequent micturition （P=0.0422）. GLIS3 rs7034200 and GRK5 rs10886471 were significantly associated with increased T2DM risk （GLIS3 rs7034200 under dominant model： P=0.0307; GRK5 rs 10886471 under recessive model： P=0.0092）. However, only the rs10886471 polymorphism in GRK5 showed a significant effect on both differentiated symptoms and T2DM risk. The C-allele was involved in both dampness-heat encumbering Pi （Spleen） syndrome （P=0.047） and qi-yin deficiency syndrome （P=0.002） via increased GRK5 expression. Conclnsions： Both T2DM and IGR exhibited its corresponding characteristic symptoms. The variants of GRK5 were involved with both qi-yin deficiency syndrome and dampness-heat encumbering Pi syndrome.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant No.82273458 to Jinfei Chen)the Start-up Fund for the Recruited Talents of the First Affiliated Hospital of Wenzhou Medical University(Grant No.2021QD025 to Jinfei Chen)。
文摘The KCNQ family of genes(KCNQ1–KCNQ5),encoding voltage-gated K+(Kv)channels,have been demonstrated to play potential pathophysiological roles in cancers.However,the associations between genetic variants located in KCNQ family genes and gastric cancer survival remain unclear.In this study,a large-scale cohort comprising 1135 Chinese gastric cancer patients was enrolled to identify genetic variants in KCNQ family genes associated with overall survival(OS).Based on the survival evaluation of all five KCNQ family genes,KCNQ1 was selected for subsequent genetic analysis.In both Cox regression model and stepwise Cox regression model used to evaluate survival-related genetic variants,we found that KCNQ1 rs10832417G>T was associated with an increased OS in gastric cancer patients(adjusted hazards ratio[HR]=0.84,95%confidence interval[CI]:0.72–0.98,P=0.023).Subsequently,a nomogram was constructed to enhance the prognostic capacity and clinical translation of rs10832417 variants.The rs10832417 T allele was predicted to increase the minimum free energy of the secondary structure.Furthermore,we observed that gastric cancer patients with downregulated KCNQ1expression had a poorer survival across multiple public datasets.The findings of the present study indicate that KCNQ1 rs10832417 may serve as an independent prognostic predictor of gastric cancer,providing novel insights into the progression and survival of the disease.
基金funded by the National Key R&D Program of China(Grant Nos.2018YFC1313100 and 2018YFC1313102)the National Natural Science Foundation of China(Grant No.81773539)+1 种基金Collaborative Innovation Center for Cancer Personalized Medicinethe Priority Academic Program Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine).
文摘Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1(C1GALT1)is known to play a critical role in the development of gastric cancer,but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer risk.By using the genome-wide association study data from the database of Genotype and Phenotype(dbGAP),we evaluated such associations with a multivariable logistic regression model and identified that the rs35999583 G>C in C1GALT1 was associated with gastric cancer risk(odds ratio,0.83;95% confidence interval[CI],0.75-0.92;P=3.95×10^(-4)).C1GALT1 mRNA expression levels were significantly higher in gastric tumor tissues than in normal tissues,and gastric cancer patients with higher C1GALT1 mRNA levels had worse overall survival rates(hazards ratio,1.33;95%CI,1.05-1.68;P_(log-rank)=1.90×10^(-2)).Furthermore,we found that C1GALT1 copy number differed in various immune cells and that C1GALT1 mRNA expression levels were positively correlated with the infiltrating levels of CD4^(+)T cells and macrophages.These results suggest that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 into a promising predictor of gastric cancer susceptibility and immune status.
文摘Inflammatory bowel diseases (IBD) are complex multifactorial disorders that include Crohn’s disease (CD) and ulcerative colitis (UC). Considering that IBD is a genetic and multifactorial disease, we screened for the distribution dynamism of IBD pathogenic genetic variants (single nucleotide polymorphisms;SNPs) and risk factors in four (4) IBD pediatric patients, by integrating both clinical exome sequencing and computational statistical approaches, aiming to categorize IBD patients in CD and UC phenotype. To this end, we first aligned genomic read sequences of these IBD patients to hg19 human genome by using bowtie 2 package. Next, we performed genetic variant calling analysis in terms of single nucleotide polymorphism (SNP) for genes covered by at least 20 read genomic sequences. Finally, we checked for biological and genomic functions of genes exhibiting statistically significant genetic variant (SNPs) by introducing Fitcon genomic parameter. Findings showed Fitcon parameter as normalizing IBD patient’s population variability, as well as inducing a relative good clustering between IBD patients in terms of CD and UC phenotypes. Genomic analysis revealed a random distribution of risk factors and as well pathogenic SNPs genetic variants in the four IBD patient’s genome, claiming to be involved in: i) Metabolic disorders, ii) Autoimmune deficiencies;iii) Crohn’s disease pathways. Integration of genomic and computational statistical analysis supported a relative genetic variability regarding IBD patient population by processing IBD pathogenic SNP genetic variants as opposite to IBD risk factor variants. Interestingly, findings clearly allowed categorizing IBD patients in CD and UC phenotypes by applying Fitcon parameter in selecting IBD pathogenic genetic variants. Considering as a whole, the study suggested the efficiency of integrating clinical exome sequencing and computational statistical tools as a right approach in discriminating IBD phenotypes as well as improving inflammatory bowel disease (IBD) molecular diagnostic process.
基金supported by the National Natural Science Foundation of China(No.81102115)2012 Chinese Nutrition Society(CNS)Nutrition Research Foundation-DSM Research Fund
文摘The present study was designed to examine the contributions of the fatty acid elongase （ELOVL） gene polymorphisms to the levels of polyunsaturated fatty acids （PUFAs） in breast milk. Two hundred and nine healthy Han Chinese mothers were included in the study. Carriers of minor alleles of SNPs （rs2397142 and rs9357760） in ELOVL5 were associated with higher levels of linoleic acid （LA）, dihomo-γ-linolenic acid （DGLA）, arachidonic acid （AA）, docosatetraenoic acid （DTA）, docosahexenoic acid （DHA）, while in rs209512 of ELOVL5 the carriers of minor alleles had lower levels of DTA compared to major homozygote alleles （P ranged from 0.004-0.046）, and genetically explained variability ranged from 3.2% for eicosapentaenoic acid （EPA） to 6.0% for LA. Our findings demonstrated that common variation in ELOVL5 gene encoding rate-limiting enzymes in the metabolism of PUFAs contribute to the PUFAs in breast milk.
文摘People living on the high plateaus of the world have long fascinated biological anthropologists and geneticists because they live in ＂thin air＂ and epitomize an extreme of human biological adaptation.
文摘Infection is the leading cause of complication after liver transplantation, causing morbidity and mortality in the first months after surgery. Allograft rejection is mediated through adaptive immunological responses, and thus immunosuppressive therapy is necessary after transplantation. In this setting, the presence of genetic variants of innate immunity receptors may increase the risk of post-transplant infection, in comparison with patients carrying wild-type alleles. Numerous studies have investigated the role of genetic variants of innate immune receptors and the risk of complication after liver transplantation, but their results are discordant. Tolllike receptors and mannose-binding lectin are arguably the most important studied molecules; however, many other receptors could increase the risk of infection after transplantation. In this article, we review the published studies analyzing the impact of genetic variants in the innate immune system on the development of infectious complications after liver transplantation.
基金This study was funded by the National Natural Science Foundation of China （No. 30571016 and No. 81072384）.
文摘Genetic variants in glioma tumor suppressor candidate region gene 1 （GLTSCR1） and ATM serine/threonine kinase （ATM） have been associated with various cancer risks. Epidemiological studies also revealed the association of variants of GLTSCR1 and ATM genes with different brain tumors. However, little is known about the relationship between both gene polymorphisms and lung cancer risk. We conducted a Chinese hospital-based casecontrol study involving 384 lung cancer cases and 387 cancer-free controls. No significant differences in the single polymorphism （GLTSCR1 rs1035938 and ATM rs11212592） association were found in five genetic models （co-dominant, dominant, recessive, overdominant and log-additive models） （adjusted by smoking duration）. Join effect of three SNPs （PPPIR13L rs1970764, CD3EAP rs967591, GLTSCR1 rs1035938） on chromosome 19q 13.3 showed that the designated haplotype2 （rs 1970764 G-rs967591 A-rs 1035938 C） [OR （95% CI）=1.60 （1.11-2.32）, P=0.012] and haplotype8 （rs 1970764 G-rs967591 G-rs 1035938 T） [OR （95% CI）=2.45 （1.17-5.12）, P=0.018] were associated with increased risk of lung cancer （adjusted by smoking duration）. The analysis ofmultifactor dimensionality reduction revealed that two 3-way models were the best fit models in analyses of 2 loci （P〈0.001） or 4 loci （P=0.015-0.016）. The entropy-based analysis indicated the strongest synergistic effect between PPPIR13L rs1970764 and ATM rs11212592 in analysis of four genes. In conclusion, our study suggests that haplotypes consisting of PPPIR13L rs1970764- CD3EAP rs967591-GLTSCR1 rs1035938 on Chr19q13.3, interaction of smoking and GLTSCR1 rs1035938-ATM rs11212592, and synergistic action of PPPIR13L rs1970764 and ATM rs 11212592 may associate with lung cancer risk in the Chinese population.
基金Superior Farms sheep producersIBEST for their supportfinancial support from the Idaho Global Entrepreneurial Mission
文摘Background Pan-genomics is a recently emerging strategy that can be utilized to provide a more comprehensive characterization of genetic variation.Joint calling is routinely used to combine identified variants across multiple related samples.However,the improvement of variants identification using the mutual support information from mul-tiple samples remains quite limited for population-scale genotyping.Results In this study,we developed a computational framework for joint calling genetic variants from 5,061 sheep by incorporating the sequencing error and optimizing mutual support information from multiple samples’data.The variants were accurately identified from multiple samples by using four steps:(1)Probabilities of variants from two widely used algorithms,GATK and Freebayes,were calculated by Poisson model incorporating base sequencing error potential;(2)The variants with high mapping quality or consistently identified from at least two samples by GATK and Freebayes were used to construct the raw high-confidence identification(rHID)variants database;(3)The high confidence variants identified in single sample were ordered by probability value and controlled by false discovery rate(FDR)using rHID database;(4)To avoid the elimination of potentially true variants from rHID database,the vari-ants that failed FDR were reexamined to rescued potential true variants and ensured high accurate identification variants.The results indicated that the percent of concordant SNPs and Indels from Freebayes and GATK after our new method were significantly improved 12%-32%compared with raw variants and advantageously found low frequency variants of individual sheep involved several traits including nipples number(GPC5),scrapie pathology(PAPSS2),sea-sonal reproduction and litter size(GRM1),coat color(RAB27A),and lentivirus susceptibility(TMEM154).Conclusion The new method used the computational strategy to reduce the number of false positives,and simulta-neously improve the identification of genetic variants.This strategy did not incur any extra cost by using any addi-tional samples or sequencing data information and advantageously identified rare variants which can be important for practical applications of animal breeding.
基金This work was financially supported by the Sci-Tech Planning Project of Jiaxing,China(2019AY32008 to BH),and the Res-Training Project of JUMC,China(JUMC2020-06 to DC).
文摘Endometriosis is defined as the presence of endometrium-like tissue outside the uterus,80%of which occur in the ovaries.It is characterized by an estrogen-dependent produces periodic and repeated bleeding,and may be accompanied by clinical symptoms such as dysmenorrhea,fatigue,dysuria,deep dyspareunia,and infertility.Due to the complex etiology and the yet-unknown pathogenesis of endometriosis,and the treatment effect is not ideal,causing significant physical and mental harm to reproductive-age women;thus,it has become a hot research topic.Endometriosis is still a mysterious disease of unknown origin and pathogenesis.Genetic factors are known to affect the manifestation and progression of endometriosis.A selection of genetic studies revealed genetic mutations and polymorphisms of endometriosis and their effects on the risk of developing this disease.This paper aimed to discuss the genetic variants associated with the risk of endometriosis and provided information to enrich the gene spectrum of endometriosis.
文摘Objective：Recent evidence indicates that dysregulation of microRNA （miRNA） biogenesis is implicated in cancer development and progression.Based on the important role of miRNA biogenesis genes in carcinogenesis,we hypothesized that genetic variations of the miRNA biogenesis genes may modulate susceptibility to cervical cancer.Methods：We identified three single nucleotide polymorphisms （SNPs） located in the 3＇-untranslated regions （3＇-UTR） of of miRNA biogenesis key genes （rs1057035 in DICER,rs3803012 in RAN and rs10773771 in HIWI） and genotyped these SNPs in a case-control study of 1,486 cervical cancer cases and 1,549 cancer-free controls in Chinese women.Results：Logistic regression analyses showed that no significant associations were observed between the three SNPs and cervical cancer risk [rs3803012 in RAN AG/GG vs.AA adjusted OR =1.104,95 ％ confidence interval （CI）：0.859-1.419; rs1057035 in DICER CT/CC vs.TT adjusted OR =0.962,95％ CI：0.805-1.149;rs10773771 in HIWICT/CC vs.TT adjusted OR =0.963,95％ CI：0.826-1.122].Conclusions：The findings did not suggest that genetic variants in the 3＇-UTR of RAN,DICER and HIWI of miRNA biogenesis genes were associated with the risk of cervical cancer in this Chinese population.
基金The current study was supported by the National Natural Science Foundation of China(Grant Nos.82130096 and 82373537)Collaborative Innovation Center for Cancer Personalized Medicine and Priority Academic Program Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine).
文摘Aberrant alternative polyadenylation(APA)events play an important role in cancers,but little is known about whether APA-related genetic variants contribute to the susceptibility to bladder cancer.Previous genome-wide association study performed APA quantitative trait loci(apaQTL)analyses in bladder cancer,and identified 17955 single nucleotide polymorphisms(SNPs).We found that gene symbols of APA affected by apaQTL-associated SNPs were closely correlated with cancer signaling pathways,high mutational burden,and immune infiltration.Association analysis showed that apaQTL-associated SNPs rs34402449 C>A,rs2683524 C>T,and rs11540872 C>G were significantly associated with susceptibility to bladder cancer(rs34402449:OR=1.355,95%confidence interval[CI]:1.159-1.583,P=1.33×10^(−4);rs2683524:OR=1.378,95%CI:1.164-1.632,P=2.03×10^(−4);rs11540872:OR=1.472,95%CI:1.193-1.815,P=3.06×10^(−4)).Cumulative effect analysis showed that the number of risk genotypes and smoking status were significantly associated with an increased risk of bladder cancer(P_(trend)=2.87×10^(−12)).We found that PRR13,being demonstrated the most significant effect on cell proliferation in bladder cancer cell lines,was more highly expressed in bladder cancer tissues than in adjacent normal tissues.Moreover,the rs2683524 T allele was correlated with shorter 3′untranslated regions of PRR13 and increased PRR13 expression levels.Collectively,our findings have provided informative apaQTL resources and insights into the regulatory mechanisms linking apaQTL-associated variants to bladder cancer risk.
基金supported by the Biological Breeding-Major Projects(2023ZD04076)the Pinduoduo-China Agricultural University Research Fund(PC2023B01012)+1 种基金the 2115 Talent Development Program of China Agricultural University,the National Natural Science Foundation of China(32201718)the Science and Technology Demonstration Project of Shandong Province(2024SFGC0402).
文摘Dear Editor,Multi-omics association analysis is a key method in crop germplasm research,helping to elucidate the regulatory mechanisms of agronomic traits(Liu et al.,2020;Liang et al.,2021).However,most existing multi-omics association studies focus on omics data under a single condition,posing challenges in identifying stress-related agronomically important genes.This difficultymainly arises fromthe increased complexity ofmulti-omics analyseswhen comparing control and stress conditions.
基金supported by the Shanghai Municipal Commission of Science and Technology Research Project(19JC1411000)the Collaborative Innovation Center Project Construction for Shanghai Women and Children’s Health.
文摘Cerebral palsy(CP)refers to a spectrum of permanent movement disorders commonly accompanied by other neurodevelopmental disorders(NDDs).CP is the most common form of physical disability in children,with an estimated prevalence of 2 to 3 per 1,000 live births worldwide,and the incidence of CP at term has not changed markedly in the past 50 years[1].The prevalence,severity,and burden of CP make it a high public health priority for prevention.Despite several reports of antenatal and perinatal risk factors for CP,determining the cause of CP remains challenging,as many children with CP have no known risk factors,and some children with risk factors do not develop CP[2].Theoretically,early interventions could improve neuroplasticity and functional outcomes,but early diagnosis of CP before a child’s first birthday requires later confirmation,which hinders early specific interventions.
基金Supported by the National Natural Science Foundation of China,No.82460940Major Project of Gansu Province Joint Fund,No.23JRRA1519+2 种基金Key Science and Technology Project of Gansu Province,No.21ZD4FA009Natural Science Foundation of Gansu Province,No.24JRRA1040Gansu Province Famous Traditional Chinese Medicine Inheritance Studio Project。
文摘Congenital scoliosis(CS)is a prevalent spinal deformity with a multifaceted etiology that remains incompletely understood.Recent advances in genetic and epigenetic research have provided novel insights into CS pathogenesis.Herein,we review the current progress in genetics and epigenetics to examine genetic variants,susceptibility factors,and the epigenetic regulatory mechanisms implicated in CS.Through an analysis of diverse genetic markers,chromosomal abnormalities,and epigenetic modifications,the correlation between genetic predisposition and environmental influences in CS pathogenesis is elucidated.By integrating these genetic and epigenetic findings,this study aims to clarify the underlying etiology of CS to provide guidance on future clinical interventions and promote the development of personalized therapeutic strategies.
基金Supported by Patronage of the Autonomous University of Nayarit,Quality Postgraduate Program with resources from the 15%Special Tax allocated to the UAN 2022.
文摘BACKGROUND MicroRNAs play a key role in regulating gene expression in human cells.Singlenucleotide variants in these molecules have been linked to cancer development,particularly breast cancer(BrC).AIM To analyze the association of three microRNA polymorphisms with the risk of BrC in women from western Mexico.METHODS This case-control study included 71 women diagnosed with BrC and 215 women without BrC.Genotypes were determined using a real-time polymerase chain reaction allelic discrimination assay.Multiple genetic models-dominant,recessive,over-dominant,additive,and multiple comparison-were applied to assess the risk.RESULTS The over-dominant model showed that the C/T genotype of MIR196A2(rs11614913)is a protective factor against the ductal histological subtype of BrC in women from western Mexico[odds ratio(OR)=0.4687,95%confidence interval(CI):0.2205-0.9963,P=0.0489].A protective effect was also observed for the C/A genotype(OR=0.2612,95%CI:0.0900-0.7582,P=0.0135)and A allele(OR=0.2826,95%CI:0.0993-0.8044,P=0.0179)of MIR618(rs2682818).No significant association was found between MIR200C(rs73262897)and BrC risk.CONCLUSION The C/T genotype of rs11614913 in MIR196A2,and C/A genotype and A allele of rs2682818 in MIR618,are associated with a protective effect against BrC in women from western Mexico.
基金supported by the National Key Research and Development Program of China(2022YFC2702700)the National Natural Science Foundation of China(No.82171586)+1 种基金Inner Mongolia Academy of Medical Sciences Public Hospital Joint Science and Technology Project(2023GLLH0045)Specific Project of Shanghai Jiao Tong University for“Invigorating Inner Mongolia through Science and Technology”(2022XYJG001-01-19).
文摘Nonobstructive azoospermia(NOA),one of the most severe types of male infertility,etiology often remains unclear in most cases.Therefore,this study aimed to detect four biallelic detrimental variants(0.5%)in the minichromosome maintenance domain containing 2(MCMDC2)genes in 768 NOA patients by whole-exome sequencing(WES).Hematoxylin and eosin(H&E)demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients(c.1360G>T,c.1956G>T,and c.685C>T)and hypospermatogenesis in one patient(c.94G>T),as further confirmed through immunofluorescence(IF)staining.The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis.The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses.The results revealed four MCMDC2 variants related to NOA,which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
基金Supported by the Ministry of Health of the People's Republic of China of Fujian Province Health Education Union Scientific(No.WKJ 2008-2-59)Provincial Natural Science Foundation of Fujian(No.2011J0133)National Natural Science Foundation of China(No.81373838)
文摘Objective： To compared the therapeutic effect of a Chinese patent medicine Naoxintong Capsule（脑心通胶囊, NXT） and aspirin with adjusted-dose warfarin in Chinese elderly patients（over 65 years） with nonvalvular atrial fibrillation（NVAF） and genetic variants of vitamin K epoxide reductase（VKORC1）, who are at high-risk of thromboembolism. Methods： A total of 151 patients, with NVAF and AA genotype of VKORC1-1639（a sensitive genotype to warfarin） and a CHA2 DS2-VASc clinical risk score of 2 or above, were chosen for this study. Patients were randomized into two groups and orally treated with a combination of aspirin（100 mg/day） and NXT（1.6 g thrice a day） or adjusted-dose warfarin [international normalized ratio 2.0–3.0）. The primary end points including ischemic stroke and death as well as the secondary end points including hemorrhage events were followed up for at least 1 year. Results： Baseline clinical data and the rates of primary end points were similar between groups. However, the rate of serious bleeding（secondary event） in the combination therapy group was lower than that in the adjusted-dose warfarin group（0% vs. 7.9%, odds ratio： 0.921, 95% confidence interval： 0.862–0.984, P=0.028）. Conclusions： Aspirin combined with NXT and warfarin displayed comparable rates of primary end point including ischemic stroke and all-cause death during the 1-year follow-up. However, as compared with warfarin, the combination therapy reduced the rate of serious bleeding. Therefore, aspirin combined with NXT might provide an alternative pharmacotherapy in preventing ischemic stroke for elderly patients with NAVF who cannot tolerate warfarin.（No. ChiC TR-TRC-13003596）
基金This work was supported by the National Natural Science Foundation of China(No.81871516,81571841)Open Research Fund of National Clinical Research Center for Geriatric Diseases(No.NCRCG-PLAGH-2018001).
文摘The development of premature coronary artery disease(PCAD)is dependent on both genetic predisposition and traditional risk factors.Strategies for unraveling the genetic basis of PCAD have evolved with the advent of modern technologies.Genome-wide association studies(GWASs)have identified a considerable number of common genetic variants that are associated with PCAD.Most of these genetic variants are attributable to lipid and blood pressure-related single-nucleotide polymorphisms(SNPs).The genetic variants that predispose individuals to developing PCAD may depend on race and ethnicity.Some characteristic genetic variants have been identified in Chinese populations.Although translating this genetic knowledge into clinical applications is still challenging,these genetic variants can be used for CAD phenotype identification,genetic prediction and therapy.In this article we will provide a comprehensive review of genetic variants detected by GWASs that are predicted to contribute to the development of PCAD.We will highlight recent findings regarding CAD-related genetic variants in Chinese populations and discuss the potential clinical utility of genetic variants for preventing and managing PCAD.
基金This work was supported by grant from National Research Centre,Egypt(Project Number 10010205).
文摘This study was performed for investigation the relationship between variants of MTP gene polymorphism and the development of NAFLD in patients with and without MS.The study was included 174 NAFLD patients(106 with MS and 68 without MS),and 141 healthy control subjects.The 493 G/T polymorphism of MTP gene was evaluated by PCR-RFLP method.The frequency of MTP TT genotype and T allele were significantly higher in NAFLD patients when compared to healthy controls.Moreover,a significant association in MTP gene polymorphism was observed in NAFLD patients with MS compared to NAFLD patients without MS and controls.Our study suggested that MTP 493 G/T gene polymorphism may act as susceptibility biomarker for NAFLD and MS.
基金Supported by the Project of Science and Technology Development of Tianjin Municipality,China(No.033113211)the Key Cultivated Academic Construction Project of State Administrative Bureau for Prophylactic Medicine of Traditional Chinese Medicine,China(No.2012)
文摘Objective： To examine the association of genetic variants with characteristic symptoms of type 2 diabetes mellitus （T2DM）. Methods： A matched case-control study was performed to investigate the association between common variants in four genes （CDKAL1, GLIS3, GRK5, and TCFTL2） and symptoms of T2DM. Symptoms were examined with questionnaire for 710 subjects. Genomic DNA was extracted from peripheral blood mononuclear cell by salting-out procedure. Genotyping was carried out by direct sequencing of the unpurified polymerase chain reaction products. Result： Most of the T2DM patients pressented characteristic symptoms, such as feeling weak in limbs （P=0.0057）, hand tremor （P=0.0208）, bradymasesis （P=0.0234）, and polyuria （P=0.0051）. Some of the T2DM patients shared characteristic symptoms, such as desire for cold drinks （P=0.0304）, polyphagia （P=0.0051）, and furred tongue （P=0.028）. The impaired glucose regulation （IGR） cases took only one characteristic symptom of frequent micturition （P=0.0422）. GLIS3 rs7034200 and GRK5 rs10886471 were significantly associated with increased T2DM risk （GLIS3 rs7034200 under dominant model： P=0.0307; GRK5 rs 10886471 under recessive model： P=0.0092）. However, only the rs10886471 polymorphism in GRK5 showed a significant effect on both differentiated symptoms and T2DM risk. The C-allele was involved in both dampness-heat encumbering Pi （Spleen） syndrome （P=0.047） and qi-yin deficiency syndrome （P=0.002） via increased GRK5 expression. Conclnsions： Both T2DM and IGR exhibited its corresponding characteristic symptoms. The variants of GRK5 were involved with both qi-yin deficiency syndrome and dampness-heat encumbering Pi syndrome.
