BACKGROUND Coronary heart disease(CHD)is a prominent cause of mortality and disability worldwide.Like most complex diseases,the risk of CHD in individuals is regulated by the interaction between genetic factors and li...BACKGROUND Coronary heart disease(CHD)is a prominent cause of mortality and disability worldwide.Like most complex diseases,the risk of CHD in individuals is regulated by the interaction between genetic factors and lifestyle.APOE and SLCO1B1 genetic polymorphisms and LPA KIV-2 copy number variation may influence the development and progression of CHD.Clarifying gene polymor-phisms can guide clinical precision and prevention,thereby improving treatment outcomes.AIM To investigate the influence of APOE and SLCO1B1 gene polymorphisms,as well as LPA KIV-2 copy number variation on CHD in the Teochew population.METHODS A total of 324 patients with CHD and 143 control participants were involved in this study.Single nucleotide polymorphisms rs429358 and rs7412 in the APOE gene,and rs2306283 and rs4149056 in the SLCO1B1 gene were analyzed via high-resolution melting curve analysis.Additionally,PCR was performed to detect KIV-2 copy number variations.Clinical risk factors and potential effects on CHD patients were subsequently assessed.RESULTS In the CHD group,the frequencies of APOE alleleε2,ε3,ε4 were 8.02%,82.97%,and 9.10%,respectively.Compared to the control groups(13.29%,79.37%,and 7.34%,respectively),theε2 allele frequency showed a significant difference(8.02%vs 13.29%,P=0.012).SLCO1B1 allele frequencies in the CHD group were not significantly different from those in the control group(*1a:26.69%vs 25.52%,*1b:61.17%vs 65.38%,*5:0.15%vs 0.35%,*15:11.83%vs 8.74%).The number of copies of the KIV-2 gene was significantly lower in the CHD group when compared to controls(23.35±8.78 vs 27.21±9.48;P<0.01).Logistic regression analysis revealed that sex,age,hypertension,diabetes,smoking,theε2 allele and KIV-2 copy number were factors influencing the presence of CHD.CONCLUSION In the Teochew population,the APOEε2 allele and a higher KIV-2 copy number were associated with a reduced risk of CHD.In contrast,the APOEε4 allele and SLCO1B1 gene were not associated with CHD.展开更多
BACKGROUND Folate metabolism gene polymorphisms may play an important role in the pathogenesis of autism spectrum disorder(ASD).However,most studies have primarily used single candidate gene typing strategies(such as ...BACKGROUND Folate metabolism gene polymorphisms may play an important role in the pathogenesis of autism spectrum disorder(ASD).However,most studies have primarily used single candidate gene typing strategies(such as targeted polymerase chain reaction technology),and current findings remain inconsistent.AIM To investigate the association of folate metabolism gene polymorphisms with ASD susceptibility and symptom severity among Chinese children.METHODS Whole-exome sequencing(WES)was conducted to systematically screen for coding region variants of key genes in the folate metabolism pathway among children with ASD,focusing on identifying polymorphisms with high mutation frequencies and potential pathogenic effects.A case-control study was then conducted to explore the association of candidate folate metabolism gene polymorphisms with the susceptibility and severity of ASD.RESULTS WES was performed on 70 children with ASD,and the case-control study included 170 children with ASD and 170 healthy controls.WES revealed that 84.3%(59/70)of children with ASD carried potentially pathogenic variants enriched in folate metabolism pathways.MTHFR C677T and MTRR A66G were significantly associated with an increased risk of ASD in both codominant and dominant models(P<0.05).The dominant model of MTRR A66G was also significantly associated with higher scores in the domains of social relations,body and object use,social and adaptive skills,total scores on the Autism Behavior Checklist,as well as emotional reactivity,nonverbal communication,and activity level on the Childhood Autism Rating Scale(P<0.05).CONCLUSION Most children with ASD carry deleterious variants in folate metabolism-related pathways.MTHFR C677T and MTRR A66G mutations are significantly associated with ASD.展开更多
BACKGROUND:Hepatitis C virus (HCV) infection is thought to be chronic and the factors leading to viral clearance or persistence are poorly understood.This study was undertaken to investigate the possibility of a signi...BACKGROUND:Hepatitis C virus (HCV) infection is thought to be chronic and the factors leading to viral clearance or persistence are poorly understood.This study was undertaken to investigate the possibility of a significant relationship between the spontaneous clearance or the persistence of hepatitis C virus (HCV) infection and cytokine and apoptosis gene polymorphisms in Tunisian patients on hemodialysis.METHODS:Polymorphisms of the genes IL-1 (-889 IL-1α,-511 and +3954 IL-1β,IL-1Ra),IL-18 (-137 and-607),IL-12 (-1188) and Apo1/Fas (-670) were determined by PCR-RFLP,PCR-SSP and PCR-VNTR in 100 healthy blood donors and 100 patients infected with HCV and undergoing hemodialysis.The patients were classified into two groups:G1 consisted of 76 active chronic hepatitis patients (positive for HCV RNA) and G2 consisted of 24 hemodialysed patients who spontaneously eliminated the virus (negative for HCV RNA).RESULTS:The frequency of genotype association [-137GC/-607CA] IL-18 was higher in G2 (41.7%) than in G1 (15.8%) (P=0.008;OR=0.26;95% CI,0.10-0.73).We also found a higher frequency of the AA genotype of the Apo1/Fas gene in G2 (41.6%) than in G1 (17.5%) (P=0.026;OR=3.49;95% CI,1.13-10.69).Adjustment for known covariate factors (age,gender and genotype) confirmed these univariate findings and revealed that the genotype association GC-CA of the (-137 and-607) IL-18 gene and the AA genotype of the Apo1/Fas gene were associated with the clearance of HCV (P=0.041 and 0.017,respectively).CONCLUSION:The two genotypes GC-CA of the (-137 and-607) IL-18 polymorphism and the AA genotype of the Apo1/Fas gene influence the outcome of HCV infection in Tunisian patients on hemodialysis.展开更多
AIM:To study the (functional) relevance of single nucleotide polymorphisms (SNPs) in genes encoding matrix metalloproteinases (MMP)-1,-2,-3,-9,tissue inhibitors of metalloproteinases (TIMP)-1,-2 and tumor necrosis fac...AIM:To study the (functional) relevance of single nucleotide polymorphisms (SNPs) in genes encoding matrix metalloproteinases (MMP)-1,-2,-3,-9,tissue inhibitors of metalloproteinases (TIMP)-1,-2 and tumor necrosis factor (TNF)-α in the etiopathogenesis of inflammatory bowel diseases (IBD),that may enhance susceptibility and/or disease severity. METHODS:Genomic DNA from 134 Crohn's disease (CD),111 ulcerative colitis (UC) patients and 248 control subjects was isolated from resected intestinal tissue or blood. Allelic composition at SNP loci was determined by PCR-RFLP or tetra primer ARMS PCR. RESULTS:The TIMP-1 genotype TT in women and T in men at SNP +372 T/C was found to increase CD susceptibility (39% vs 23.8%,P=0.018 and 67.9% vs 51.6%,P=0.055,respectively),while women with this genotype were less prone to development of fistulae during follow-up (41.4% vs 68.3%,P=0.025). Male IBD or CD patients carrying the TIMP-1 +372 T-allele expressed lower levels of TIMP-1 in surgically resected macroscopically inflamed tissue (0.065 < P < 0.01). The 5T5T genotype at MMP-3 SNP -1613 5T/6T increased the chance of stenotic complications in CD during follow-up (91.2% vs 71.8%,P = 0.022) but seemed to protect against colonic involvement of this disease at first endoscopic/radiologic examination (35.3% vs 59.5%,P=0.017). CONCLUSION:Allelic composition at the examinedSNPs in genes coding for TIMP-1 and MMP-3 affect CD susceptibility and/or phenotype,i.e.,fistulizing disease,stricture pathogenesis and first disease localisation. These findings reinforce the important role of these proteins in IBD.展开更多
AIM: To investigate the effects of interleukin-8 (IL-8 ), macrophage migration inhibitory factor (MIF ) gene polymorphisms, Helicobacter pylori (H. pylori ) infection, on the risk of developing severe chronic atrophic...AIM: To investigate the effects of interleukin-8 (IL-8 ), macrophage migration inhibitory factor (MIF ) gene polymorphisms, Helicobacter pylori (H. pylori ) infection, on the risk of developing severe chronic atrophic gastritis (SCAG) and intestinal metaplasia (IM). METHODS: A total of 372 cases were selected from a cohort study in Linqu County, a high risk area for gastric cancer (GC) in northern China. To obtain a sufficient group size, patients with normal or superficial gastritis were included. Based on an average follow-up period of 56 mo, the 372 cases were divided into no progres-sion group (no histological progression from normal or superficial gastritis, n = 137), group Ⅰ (progressed from normal or superficial gastritis to SCAG, n = 134) and group Ⅱ (progressed from normal or superficial gastritis to IM, n = 101). IL-8 , MIF gene polymorphisms were detected by polymerase chain reaction-based denaturing high-performance liquid chromatography analysis and DNA sequencing. RESULTS: An increased risk of SCAG was found in subjects with IL-8-251 AA genotype [odds ratio (OR) = 2.62, 95% CI: 1.23-5.72] or IL-8-251 A allele carriers (AA + AT) (OR = 1.81, 95% CI: 1.06-3.09). An elevated risk of IM was found in subjects with IL-8-251 AT genotype (OR = 2.27, 95% CI: 1.25-4.14) or IL-8-251 A allele carriers (OR = 2.07, 95% CI: 1.16-3.69). An increased risk of SCAG was found in subjects with MIF-173 GC genotype (OR = 2.36, 95% CI: 1.38-4.02) or MIF-173 C allele carriers (GC + CC) (OR = 2.07, 95% CI: 1.21-3.55). An elevated risk of IM was found in subjects with MIF-173 CC genotype (OR = 2.27, 95% CI: 1.16-4.46) or MIF-173 C allele carriers (OR = 3.84, 95% CI: 1.58-9.34). The risk of SCAG and IM was more evident in subjects carrying IL-8-251 A allele (OR = 6.70, 95% CI: 1.29-9.78) or MIF-173 C allele (OR = 6.54, 95% CI: 2.97-14.20) and positive for H. pylori infection. CONCLUSION: IL-8-251 and MIF-173 gene polymorphisms are significantly associated with the risk of SCAG and IM in a population with a high risk of GC in Linqu County, Shandong Province, China.展开更多
Evidence suggests that interleukin-10（IL-10） deficiency exacerbates inflammation and worsens the outcome of brain ischemia. In view of the critical role of the single nucleotide polymorphic sites-1082（A/G） and-819...Evidence suggests that interleukin-10（IL-10） deficiency exacerbates inflammation and worsens the outcome of brain ischemia. In view of the critical role of the single nucleotide polymorphic sites-1082（A/G） and-819（C/T） in the promoter region of the IL-10 gene, we hypothesized that they are associated with cerebral infarction morbidity in the Chinese Han population. We genotyped these allelic gene polymorphisms by amplification refractory mutation system-polymerase chain reaction methods in 181 patients with cerebral infarction（cerebral infarction group） and 115 healthy subjects（control group）. We identified significant differences in genotype distribution and allele frequency of the IL-10-1082 A/G allele between cerebral infarction and control groups（χ2 = 6.643, P = 0.010）. The IL-10-1082 A allele frequency was significantly higher in the cerebral infarction group（92.3%） than in the control group（86.1%）（P = 0.015）. Moreover, cerebral infarction risk of the AA genotype was 2-fold higher than with the AG genotype（OR = 2.031, 95%CI： 1.134-3.637）. In addition, AA genotype together with hypertension was the independent risk factor of cerebral infarction（OR = 2.073, 95%CI： 1.278-3.364）. No statistical difference in genotype distribution or allele frequency of IL-10-819 C/T was found between cerebral infarction and control groups（P 〉 0.05）. These findings suggest that the IL-10-1082 A/G gene polymorphism is involved in cerebral infarction, and increased A allele frequency is closely associated with occurrence of cerebral infarction.展开更多
AIM:Phase I/II enzymes metabolize environmental carcinogens and several functional polymorphisms have been reported in their encoding genes. Although their significance with regard to esophageal carcinogenicity has be...AIM:Phase I/II enzymes metabolize environmental carcinogens and several functional polymorphisms have been reported in their encoding genes. Although their significance with regard to esophageal carcinogenicity has been examined epidemiologically, it remains controversial. The present systematic review of the literature was performed to clarify associations. METHODS: Eligible studies were case-control or cohort studies published until September 2004 that were written in any language. From PubMed and a manual review of reference lists in relevant review articles, we obtained 16 studies related to the CYP1A1 Ile-Val substitution in exon 7, CYP1A1 MspI polymorphisms, CYP2E1 Rsal polymorphisms, GSTM1 null type, GSTT1 null type and GSTP1 Ilel04Val. All were of case-control design. Summary statistics were odds ratios (ORs) comparing heterozygous-, homozygous-non-wild type or these two in combination with the homozygous wild type, or the null type with the non-null type for GSTM1 and GSTT1, A random effect model was used to estimate the summary ORs. A meta-regression analysis was applied to explore sources of heterogeneity. RESULTS: Individuals with the Ile-Val substitution in CYP1A1 exon 7 had increased esophageal cancer risk, with ORs (95%CI) compared with lie/lie of 1.37 (1.09-1.71), 2.52 (1.62-3.91) and 1.44 (1.17-1.78) for Ile-Val, Val/Val genotype and the combined group. No significant association was found between esophageal cancer risk and the other genetic parameters. CONCLUSION: A significant association exists between the CYP1A1 Ile-Val polymorphism and risk of esophageal cancer. Polymorphisms that increase the internal exposure to activated carcinogens may increase the risk of esophageal cancer.展开更多
Objective： To investigate the relationships between endothelial nitric oxide synthases （eNOS） G894T and 27 bpvariable number tandem repeat （VNTR） gene polymorphisms and osteoporosis in the postmenopausal women of...Objective： To investigate the relationships between endothelial nitric oxide synthases （eNOS） G894T and 27 bpvariable number tandem repeat （VNTR） gene polymorphisms and osteoporosis in the postmenopausal women of Chinese Han nationality. Methods： In the present study, 281 postmenopausal women from Xi＇an urban area in West China were recruited, and divided into osteoporosis, osteopenia, and normal groups according to the diagnostic criteria of osteoporosis proposed by World Health Organization （WHO）. The bone mineral density （BMD） values of lumbar vertebrae and left hips were determined by QDR-2000 dual energy X-ray absorptiometry. Blood samples were tested for plasma biochemical indicators including testosterone, estradiol, calcitonin, osteocalcin, and procollagen type I amino-terminal propeptide by enzyme-linked immunosorbent assay （ELISA）, tartrate-resistant acid phosphatase by spectrophotometric method, and the content of nitric oxide by Griess method. Genome DNA was extracted from whole blood, and G894T polymorphism of eNOS gene was analyzed by using polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） method and 27 bp-VNTR polymorphism of eNOS gene was genotyped by PCR method. Then the relationships between genotypes and biochemical indicators, genotypes and osteoporosis, and haplotypes and osteoporosis were analyzed. Results： The average BMD values of the femoral neck, ward＇s triangle and lumbar vertebrae 1-4 （LI-L4） in the subjects with T/T genotype in eNOS G894T locus were significantly higher than those in the subjects with G/T and G/G genotypes （P〈0.05）. The average BMD of the femoral neck in the subjects with a/a genotype of eNOS 27 bp-VNTR locus was evidently higher than that in the subjects with b/b genotype （P〈0.05）. The plasma testosterone and osteocalcin concentrations in the subjects of eNOS G894T G/T genotype were evidently higher than those in the subjects of other genotypes （P〈0.05）; the plasma estradiol concentration in the subjects of eNOS 27 bp-VNTR a/a genotype was obviously higher than that in the subjects of b/b genotype （P〈0.01）. eNOS G/G homozygous frequencies in osteoporosis women, osteopenia women, and normal women were 85.37%, 76.38%, and 83.87%, respectively （P〉0.05）. 0% osteoporosis woman, 0.79% osteopenia women, and 3.23% normal women were eNOS a/a homozygous （P〈0.05）. The frequencies of eNOS 27 bp-VNTR a allele were 5.33% in the osteoporosis group, 10.24% in the osteopenia group, and 16.13% in the normal group （P〈0.05, odds ratio （OR）=0.29, 95% confidence interval （CI）=0.11-0.77）, suggesting that a/a genotype and a allele might have protective effects on osteoporosis. The haplotype analysis showed that G-b was 87.7% （214/244） in the osteoporosis group （P〈0.05, OR=2.48, 95% CI=1. 18-5.18）. G-a was 5.3% （13/244） in the osteoporosis group （P〈0.05, OR=0.29, 95% CI=0. 11-0.77）. G-b was a risk factor for osteoporosis, and G-a a protective factor. Conclusion： eNOS G894T G/T genotype influenced the plasma testosterone and osteocalcin concentrations, and T/T genotype influenced BMD. eNOS 27 bp-VNTR a/a genotype increased plasma estradiol concentration to have a protective effect on osteoporosis.展开更多
Latin America shows one of the highest incidence rates of gastric cancer in the world,with variations in mortality rates among nations or even within countries belonging to this region.Gastric cancer is the result of ...Latin America shows one of the highest incidence rates of gastric cancer in the world,with variations in mortality rates among nations or even within countries belonging to this region.Gastric cancer is the result of a multifactorial complex process,for which a multistep model of carcinogenesis is currently accepted.Additionally to the infection with Helicobacter pylori,that plays a major role,environmental factors as well as genetic susceptibility factors are significant players at different stages in the gastric cancer process.The differences in population origin,demographic structure,socio-economic development,and the impact of globalization lifestyles experienced in Latin America in the last decades,all together offer opportunities for studying in this context the influence of genetic polymorphisms in the susceptibility to gastric cancer.The aim of this article is to discuss current trends on gastric cancer in Latin American countries and to review the available published information about studies of association of gene polymorphisms involved in gastric cancer susceptibility from this region of the world.A total of 40 genes or genomic regions and69 genetic variants,58%representing markers involved in inflammatory response,have been used in a number of studies in which predominates a low number of individuals(cases and controls)included.Polymorphisms of IL-1B(-511 C/T,14 studies;-31 T/C,10 studies)and IL-1RN(variable number of tandem repeats,17 studies)are the most represented ones in the reviewed studies.Other genetic variants recently evaluated in large metaanalyses and associated with gastric cancer risk were also analyzed in a few studies[e.g.,prostate stem cell antigen(PSCA),CDH1,Survivin].Further and better analysis centered in gene polymorphisms linked to other covariates,epidemiological studies and the information provided by meta-analyses and genome-wide association studies should help to improve our understanding of gastric cancer etiology in order to develop appropriate health programs in Latin America.展开更多
BACKGROUND:New-onset diabetes after transplantation(NODAT) has become one of the major factors that affect the overall survival and long-term life quality in liver transplantation(LT) recipients. Previous studies foun...BACKGROUND:New-onset diabetes after transplantation(NODAT) has become one of the major factors that affect the overall survival and long-term life quality in liver transplantation(LT) recipients. Previous studies found that the serum adiponectin concentration of diabetic patients is significantly lower than that of healthy subjects. Adiponectin regulates the blood glucose level by increasing body sensitivity to insulin through various mechanisms. In this study, we aimed to investigate the impact of diabetes related gene polymorphisms on the development of NODAT in liver recipients.METHODS:A total of 256 LT patients in a single-center were selected retrospectively for the study. Genomic DNA was extracted from explanted liver tissues, and tested for twelve diabetes mellitus associated single nucleotide polymorphisms by Sequenom Mass ARRAY. Modified clinical models in predicting NODAT were established and evaluated.RESULTS:The GG genotype of ADIPOQ rs1501299 gene polymorphism was significantly more frequent in NODAT than non-NODAT LT patients(56% vs 39%, P=0.014). Dominant model(GG vs GT+TT, P=0.030) and recessive model(GT+GG vs TT, P=0.005) also confirmed the genotype distribution difference between NODAT and non-NODAT groups. Age(OR=1.048, P=0.004), BMI(OR=1.107, P=0.041), and blood tacrolimus level at 1-month LT(OR=1.170, P=0.003) were clinical independent risk factors of NODAT. Furthermore, rs1501299 could improve the ability of clinical model in predicting NODAT(AUROC=0.743, P<0.001).CONCLUSION:ADIPOQ rs1501299 gene polymorphism is associated with an increased risk of NODAT, which should be added to the clinical models in predicting the occurrence of NODAT in LT recipients.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
AIM To investigate the role of genetic variants of angiotensin converting enzyme(ACE) and angiotensinogen(AGT) genes in the antiproteinuric efficacy of ACE inhibitor therapy in diabetic nephropathy(DN) patients.METHOD...AIM To investigate the role of genetic variants of angiotensin converting enzyme(ACE) and angiotensinogen(AGT) genes in the antiproteinuric efficacy of ACE inhibitor therapy in diabetic nephropathy(DN) patients.METHODS In the present study, 270 type 2 diabetes mellitus patients with nephropathy were enrolled and treated with ACE inhibitor(ramipril) and followed at 6 mo for renal function and albumin excretion by estimating serum creatinine, end stage renal disease, and albumin/creatinine ratio(ACR) in urine. Genotyping of ACE I/D and AGT M235 T polymorphisms were performed by using primer specific polymerase chain reaction(PCR) and PCR-RFLP techniques, respectively. RESULTS Forty-eight percent of DN patients(responders) benefited with respect to proteinuria from ACE inhibitor therapy at 6 mo follow-up. A significant reduction in ACR was observed after 6 mo treatment with ACE inhibitor irrespective of whether DN patients were micro-albuminuric(≥ 30 and < 300 mg/g creatinine) or macro-albuminuric(≥ 300 mg/g creatinine) at the time of enrollment. However, macro-albuminuric patients(55%) showed better response to therapy. A reduction in urinary ACR was found independent of genotypes of ACE I/D and AGT M235 T polymorphisms although macro-albuminuric patients having TT genotype showed statistically insignificant increased response(72%). CONCLUSION ACE inhibitor therapy reduced urinary ACR by ≥ 30% in 50% of DN patients and the response is independent of ACE I/D and AGT M235 T polymorphisms.展开更多
Dear editor, P-glycoprotein （P-gp, also known as ATP-binding cassette transport sub-family B member 1, ABCB1） is a potent ATP-dependent efflux pump for a wide variety of drugs. Although studies of its substrates are...Dear editor, P-glycoprotein （P-gp, also known as ATP-binding cassette transport sub-family B member 1, ABCB1） is a potent ATP-dependent efflux pump for a wide variety of drugs. Although studies of its substrates are abundant [ 1, 2], and ABCB1 is a well-conserved gene, there is increasing evi- dence that its polymorphisms affect substrate specificity [3]. A previous study reported that the synonymous single nucleotide polymorphism （SNP） C3435T （rs1045642） affects the timing of co-translational folding and insertionof P-gp into the membrane,展开更多
Objectives Apolipoprotein(Apo) A5 gene poly-morphisms and alcohol consumption have been associated with increased serum triglyceride(TG) levels,but little is known about their interactions on serum lipid levels.The pr...Objectives Apolipoprotein(Apo) A5 gene poly-morphisms and alcohol consumption have been associated with increased serum triglyceride(TG) levels,but little is known about their interactions on serum lipid levels.The present study was undertaken polymorphismsand alcohol consumption on serum lipid levels.Methods A total of 516 unrelated nondrinkers and 514 drinkers aged 15 -89 were randomly selected from our previous stratified randomized cluster samples.Genotyping of the ApoA5was performed by polymerase chain reaction and restriction fragment length polymorphism,and then confirmed by direct sequencing.Interactions of the ApoA5alcohol consumption were assessed by using a cross-product term between genotypes and the aforementioned factor.Results The levels of total cholesterol (TC),TG,high-density lipoprotein cholesterol(HDL-C), ApoA1 and ApoB were higher in drinkers than in nondrinkers (P【0.05-0.001).The genotypic and allelic frequencies of the three single nucleotide polymorphisms(SNPs) were not different between the two groups.The levels of TG in non-drinkers, and TC,TG,low-density lipoprotein cholesterol (LDL-C)and ApoB in drinkers were different among the three -1131T】C genotypes(P【0.05-0.001).The -1131C allele carriers had higher serum TC,TG,LDL-C and ApoB levels than the allele noncarriers.The levels of TG,HDL-C and ApoB in nondrinkers,and TG and HDL-C in drinkers were different between the two c.553G】T genotypes(P【0.05-0.01).The C.553T allele carriers had higher serum TG and ApoB levels,and lower HDL-C levels than the allele noncarriers.Serum lipid levels in nondrinkers were not different among the three c.457G】A genotypes(P【0.05 for all), but the levels of HDL-C,LDL-C,ApoA1 and ApoB in drinkers were different between the GG and GA/AA geno-types (P【0.05-0.001).The C.457A allele carriers had lower serum HDL-C,LDL-C,ApoAl and ApoB levels than the allele noncarriers.We also observed four haplotypes:G-G-T, G-G-C,G-A-T,and T-G-C with frequencies ranging from 0.06 to 0.87,representing 100%of all haplotypes in the both populations.The ApoA5 haplotypes were significantly(P【0.05) associated at the global level with TC,TG,HDL-C, LDL-C,Apo1,and ApoB,even after correction for multiple testing with permutation test.In particular,carriers of haplo-type G-G-C had significantly higher TC,TG,LDL-C,ApoB than noncarriers,whereas carriers of haplotype C-A-T had significantly lower TC,LDL-C,ApoAl and ApoB,and higher HDL-C than noncarriers.Serum TC levels in nondrinkers were correlated with -1131T】C genotype and allele(P【0.05 for each),whereas serum TC,TG and LDL-C levels in drinkers were associated with -1131 T】C and C.553G】T genotypes,or c.457G】A alleles(P【0.05-0.001).Serum lipid parameters were also correlated with several environmental factors in the both groups.Conclusions The differences in serum lipid profiles between the drinkers and nondrinkers might partly result from different interactions of ApoA5 gene polymor phisms and alcohol consumption.genotypes and -1131T】C, c.553G】T and c.457G】A to detect the interactions of the ApoA5展开更多
BACKGROUND:Genetic variations of the 5-lipoxygenase activating protein and leukotriene A4 hydrolase genes that confer an increased risk of ischemic stroke have implicated the family of leukotrienes as potential mediat...BACKGROUND:Genetic variations of the 5-lipoxygenase activating protein and leukotriene A4 hydrolase genes that confer an increased risk of ischemic stroke have implicated the family of leukotrienes as potential mediators of ischemic stroke.This study aimed to explore the association of ALOX5,LTA4 H and LTC4 S gene polymorphisms with ischemic stroke risk in a cohort of Chinese in east China.METHODS:This case-control study consisted of 690 patients with ischemic stroke and 690 controls.Polymorphisms of ALOX5 rs2029253 A/G,LTA4 H rs6538697 T/C,and LTC4 S rs730012 A/C were genotyped by the polymerase chain reaction and restriction fragment length polymorphism(PCR-RFLP) analysis.The multivariate logistic regression model was used to exclude the effects of conventional risk factors on ischemic stroke.RESULTS:Carriers of C allele in rs730012 were more susceptible to ischemic stroke(OR:1.37;95%CI:1.08-1.73;P=0.009).The rs2029253 GG genotype showed a risk-reducing effect on ischemic stroke(OR:0.72;95%CI:0.55-0.93;P=0.013) while the rs6538697 CC genotype had an increased risk of ischemic stroke(OR:1.77;95%CI:1.09-2.89;P=0.022).The rs730012 variant was not associated with ischemic stroke risk after adjusting confounding factors(P>0.05).CONCLUSION:The present study suggested that gene polymorphisms in the leukotrienes pathway may exert influences,with independent genetic effects,on ischemic stroke susceptibility in a cohort of Chinese in east China.展开更多
Developmental dyslexia is a complex reading and writing disorder with strong genetic components. In previous genetic studies about dyslexia, a number of candidate genes have been identified. These include DCDC2, which...Developmental dyslexia is a complex reading and writing disorder with strong genetic components. In previous genetic studies about dyslexia, a number of candidate genes have been identified. These include DCDC2, which has repeatedly been associated with developmental dyslexia in various European and American populations. However, data regarding this relationship are varied according to population. The Uyghur people of China represent a Eurasian population with an interesting genetic profile. Thus, this group may provide useful information about the association between DCDC2 gene polymorphisms and dyslexia. In the current study, we examined genetic data from 392 Uyghur children aged 8–12 years old from the Xinjiang Uyghur Autonomous Region of China. Participants included 196 children with dyslexia and 196 grade-, age-, and gender-matched controls. DNA was isolated from oral mucosal cell samples and fourteen single nucleotide polymorphisms（rs6456593, rs1419228, rs34647318, rs9467075, rs793862, rs9295619, rs807701, rs807724, rs2274305, rs7765678, rs4599626, rs6922023, rs3765502, and rs1087266） in DCDC2 were screened via the SNPscan method. We compared SNP frequencies in five models（Codominant, Dominant, Recessive, Heterozygote advantage, and Allele） between the two groups by means of the chi-squared test. A single-locus analysis indicated that, with regard to the allele frequency of these polymorphisms, three SNPs（rs807724, rs2274305, and rs4599626） were associated with dyslexia. rs9467075 and rs2274305 displayed significant associations with developmental dyslexia under the dominant model. rs6456593 and rs6922023 were significantly associated with developmental dyslexia under the dominant model and in the heterozygous genotype. Additionally, we discovered that the T-G-C-T of the four-marker haplotype（rs9295619-rs807701-rs807724-rs2274305） and the T-A of the two-marker haplotype（rs3765502-1087266） were significantly different between cases and controls. Thus, we conclude that DCDC2 gene polymorphisms are associated with developmental dyslexia in Chinese Uyghur children.展开更多
Coronary heart disease （CHD） is a major health problem in many countries and its pathogenesis is not yet fully understood, contributing to significant morbidity and mortality. Accumulated evidence manifest clearly t...Coronary heart disease （CHD） is a major health problem in many countries and its pathogenesis is not yet fully understood, contributing to significant morbidity and mortality. Accumulated evidence manifest clearly that CHD is determined by a complex interplay of genetic and environmental factors. Many clinical data have showed that the renin-angiotensin system （RAS） hypertension and CHD involved in many cardiovascular diseases, such as Angiotensinogen （AGT） is the key components of the RAS system, and two gene polymorphisms of AGT had been detected of the CHD risk： M235T and T174M. This article reviews the effects of AGT gene polymorphisms on the CHD.展开更多
Objective Coronary heart disease （CHD） is a multifactorial disease. This meta-analysis was performed to evaluate the relationship between angiotensinogen gene polymorphisms and CHD in the Chinese population. Methods...Objective Coronary heart disease （CHD） is a multifactorial disease. This meta-analysis was performed to evaluate the relationship between angiotensinogen gene polymorphisms and CHD in the Chinese population. Methods We searched literature in pubmed （1990- 2010.8） and CNKI （1990-2010.8） for all the relevant studies on 2 angiotensinogen polymorphisms （M235T and T174M） and risk of CHD. The meta-analysis software Stata 10.0 was used for ascertaining heterogeneity among individual studies and for combining all the studies. Furthermore,Egger＇s test and sensitivity analysis were performed to insure authenticity of the outcome.Results Ten associations studies on 2 angiotensinogen polymorphisms （M235T and T174M） were included in this meta-analysis. In a combined analysis, the summary per-allele odds ratio for CHD of the M235T polymorphism was 1.374 （95% confidence interval, 1.019 to 1.852） and T174M polymorphism was 4.089 （95% confidence interval, 1.697 to 9.851）. Conclusions The M235T polymorphism had weak but statistically significant association with CHD while the T174M polymorphism was more strongly associated with a CHD risk in Chinese population, but further confirmation studies are needed展开更多
Essential hypertension is one of the most common multi- factorial diseases, affecting 20%--30% of the human popula- tion （Ibrahim and Damasceno, 2012）. Based on the results of twin studies, adoption studies and stat...Essential hypertension is one of the most common multi- factorial diseases, affecting 20%--30% of the human popula- tion （Ibrahim and Damasceno, 2012）. Based on the results of twin studies, adoption studies and statistical analyses of blood pressure （BP） across various pedigrees, it has been estimated that 30%--50% of the variability in blood pressure among the general population is genetically determined （Garcia et al., 2003）. Although the genetic mechanisms of essential hyper- tension have not been studied well, investigations for the genes that constitute the renin-angiotensin system （RAS） appear to be particularly promising, since this system plays a central role in the regulation of blood pressure （Ferrario, 2010）.展开更多
基金Supported by Special Research Plan 2023 of Chaozhou,No.202303GY05。
文摘BACKGROUND Coronary heart disease(CHD)is a prominent cause of mortality and disability worldwide.Like most complex diseases,the risk of CHD in individuals is regulated by the interaction between genetic factors and lifestyle.APOE and SLCO1B1 genetic polymorphisms and LPA KIV-2 copy number variation may influence the development and progression of CHD.Clarifying gene polymor-phisms can guide clinical precision and prevention,thereby improving treatment outcomes.AIM To investigate the influence of APOE and SLCO1B1 gene polymorphisms,as well as LPA KIV-2 copy number variation on CHD in the Teochew population.METHODS A total of 324 patients with CHD and 143 control participants were involved in this study.Single nucleotide polymorphisms rs429358 and rs7412 in the APOE gene,and rs2306283 and rs4149056 in the SLCO1B1 gene were analyzed via high-resolution melting curve analysis.Additionally,PCR was performed to detect KIV-2 copy number variations.Clinical risk factors and potential effects on CHD patients were subsequently assessed.RESULTS In the CHD group,the frequencies of APOE alleleε2,ε3,ε4 were 8.02%,82.97%,and 9.10%,respectively.Compared to the control groups(13.29%,79.37%,and 7.34%,respectively),theε2 allele frequency showed a significant difference(8.02%vs 13.29%,P=0.012).SLCO1B1 allele frequencies in the CHD group were not significantly different from those in the control group(*1a:26.69%vs 25.52%,*1b:61.17%vs 65.38%,*5:0.15%vs 0.35%,*15:11.83%vs 8.74%).The number of copies of the KIV-2 gene was significantly lower in the CHD group when compared to controls(23.35±8.78 vs 27.21±9.48;P<0.01).Logistic regression analysis revealed that sex,age,hypertension,diabetes,smoking,theε2 allele and KIV-2 copy number were factors influencing the presence of CHD.CONCLUSION In the Teochew population,the APOEε2 allele and a higher KIV-2 copy number were associated with a reduced risk of CHD.In contrast,the APOEε4 allele and SLCO1B1 gene were not associated with CHD.
基金Supported by the National Key Research and Development Program of China,No.2024YFC2707801the Science and Technology Innovation Commission of Shenzhen,No.JCYJ20230807143800002.
文摘BACKGROUND Folate metabolism gene polymorphisms may play an important role in the pathogenesis of autism spectrum disorder(ASD).However,most studies have primarily used single candidate gene typing strategies(such as targeted polymerase chain reaction technology),and current findings remain inconsistent.AIM To investigate the association of folate metabolism gene polymorphisms with ASD susceptibility and symptom severity among Chinese children.METHODS Whole-exome sequencing(WES)was conducted to systematically screen for coding region variants of key genes in the folate metabolism pathway among children with ASD,focusing on identifying polymorphisms with high mutation frequencies and potential pathogenic effects.A case-control study was then conducted to explore the association of candidate folate metabolism gene polymorphisms with the susceptibility and severity of ASD.RESULTS WES was performed on 70 children with ASD,and the case-control study included 170 children with ASD and 170 healthy controls.WES revealed that 84.3%(59/70)of children with ASD carried potentially pathogenic variants enriched in folate metabolism pathways.MTHFR C677T and MTRR A66G were significantly associated with an increased risk of ASD in both codominant and dominant models(P<0.05).The dominant model of MTRR A66G was also significantly associated with higher scores in the domains of social relations,body and object use,social and adaptive skills,total scores on the Autism Behavior Checklist,as well as emotional reactivity,nonverbal communication,and activity level on the Childhood Autism Rating Scale(P<0.05).CONCLUSION Most children with ASD carry deleterious variants in folate metabolism-related pathways.MTHFR C677T and MTRR A66G mutations are significantly associated with ASD.
基金supported by a grant from the Tunisian Kidney Transplantation Research Fund
文摘BACKGROUND:Hepatitis C virus (HCV) infection is thought to be chronic and the factors leading to viral clearance or persistence are poorly understood.This study was undertaken to investigate the possibility of a significant relationship between the spontaneous clearance or the persistence of hepatitis C virus (HCV) infection and cytokine and apoptosis gene polymorphisms in Tunisian patients on hemodialysis.METHODS:Polymorphisms of the genes IL-1 (-889 IL-1α,-511 and +3954 IL-1β,IL-1Ra),IL-18 (-137 and-607),IL-12 (-1188) and Apo1/Fas (-670) were determined by PCR-RFLP,PCR-SSP and PCR-VNTR in 100 healthy blood donors and 100 patients infected with HCV and undergoing hemodialysis.The patients were classified into two groups:G1 consisted of 76 active chronic hepatitis patients (positive for HCV RNA) and G2 consisted of 24 hemodialysed patients who spontaneously eliminated the virus (negative for HCV RNA).RESULTS:The frequency of genotype association [-137GC/-607CA] IL-18 was higher in G2 (41.7%) than in G1 (15.8%) (P=0.008;OR=0.26;95% CI,0.10-0.73).We also found a higher frequency of the AA genotype of the Apo1/Fas gene in G2 (41.6%) than in G1 (17.5%) (P=0.026;OR=3.49;95% CI,1.13-10.69).Adjustment for known covariate factors (age,gender and genotype) confirmed these univariate findings and revealed that the genotype association GC-CA of the (-137 and-607) IL-18 gene and the AA genotype of the Apo1/Fas gene were associated with the clearance of HCV (P=0.041 and 0.017,respectively).CONCLUSION:The two genotypes GC-CA of the (-137 and-607) IL-18 polymorphism and the AA genotype of the Apo1/Fas gene influence the outcome of HCV infection in Tunisian patients on hemodialysis.
基金grant WS98-17 from the Netherlands Digestive Diseases Foundation
文摘AIM:To study the (functional) relevance of single nucleotide polymorphisms (SNPs) in genes encoding matrix metalloproteinases (MMP)-1,-2,-3,-9,tissue inhibitors of metalloproteinases (TIMP)-1,-2 and tumor necrosis factor (TNF)-α in the etiopathogenesis of inflammatory bowel diseases (IBD),that may enhance susceptibility and/or disease severity. METHODS:Genomic DNA from 134 Crohn's disease (CD),111 ulcerative colitis (UC) patients and 248 control subjects was isolated from resected intestinal tissue or blood. Allelic composition at SNP loci was determined by PCR-RFLP or tetra primer ARMS PCR. RESULTS:The TIMP-1 genotype TT in women and T in men at SNP +372 T/C was found to increase CD susceptibility (39% vs 23.8%,P=0.018 and 67.9% vs 51.6%,P=0.055,respectively),while women with this genotype were less prone to development of fistulae during follow-up (41.4% vs 68.3%,P=0.025). Male IBD or CD patients carrying the TIMP-1 +372 T-allele expressed lower levels of TIMP-1 in surgically resected macroscopically inflamed tissue (0.065 < P < 0.01). The 5T5T genotype at MMP-3 SNP -1613 5T/6T increased the chance of stenotic complications in CD during follow-up (91.2% vs 71.8%,P = 0.022) but seemed to protect against colonic involvement of this disease at first endoscopic/radiologic examination (35.3% vs 59.5%,P=0.017). CONCLUSION:Allelic composition at the examinedSNPs in genes coding for TIMP-1 and MMP-3 affect CD susceptibility and/or phenotype,i.e.,fistulizing disease,stricture pathogenesis and first disease localisation. These findings reinforce the important role of these proteins in IBD.
基金Supported by The Grants from Beijing Municipal Science Foundationthe Key Technology Research and Development Program, No. 2002BA711A06+1 种基金the National 973 Project, No.1998051203863 Project, No. 2006A402
文摘AIM: To investigate the effects of interleukin-8 (IL-8 ), macrophage migration inhibitory factor (MIF ) gene polymorphisms, Helicobacter pylori (H. pylori ) infection, on the risk of developing severe chronic atrophic gastritis (SCAG) and intestinal metaplasia (IM). METHODS: A total of 372 cases were selected from a cohort study in Linqu County, a high risk area for gastric cancer (GC) in northern China. To obtain a sufficient group size, patients with normal or superficial gastritis were included. Based on an average follow-up period of 56 mo, the 372 cases were divided into no progres-sion group (no histological progression from normal or superficial gastritis, n = 137), group Ⅰ (progressed from normal or superficial gastritis to SCAG, n = 134) and group Ⅱ (progressed from normal or superficial gastritis to IM, n = 101). IL-8 , MIF gene polymorphisms were detected by polymerase chain reaction-based denaturing high-performance liquid chromatography analysis and DNA sequencing. RESULTS: An increased risk of SCAG was found in subjects with IL-8-251 AA genotype [odds ratio (OR) = 2.62, 95% CI: 1.23-5.72] or IL-8-251 A allele carriers (AA + AT) (OR = 1.81, 95% CI: 1.06-3.09). An elevated risk of IM was found in subjects with IL-8-251 AT genotype (OR = 2.27, 95% CI: 1.25-4.14) or IL-8-251 A allele carriers (OR = 2.07, 95% CI: 1.16-3.69). An increased risk of SCAG was found in subjects with MIF-173 GC genotype (OR = 2.36, 95% CI: 1.38-4.02) or MIF-173 C allele carriers (GC + CC) (OR = 2.07, 95% CI: 1.21-3.55). An elevated risk of IM was found in subjects with MIF-173 CC genotype (OR = 2.27, 95% CI: 1.16-4.46) or MIF-173 C allele carriers (OR = 3.84, 95% CI: 1.58-9.34). The risk of SCAG and IM was more evident in subjects carrying IL-8-251 A allele (OR = 6.70, 95% CI: 1.29-9.78) or MIF-173 C allele (OR = 6.54, 95% CI: 2.97-14.20) and positive for H. pylori infection. CONCLUSION: IL-8-251 and MIF-173 gene polymorphisms are significantly associated with the risk of SCAG and IM in a population with a high risk of GC in Linqu County, Shandong Province, China.
基金supported by the National Natural Science Foundation of ChinaNo.81171867+1 种基金a grant from the Key Research Program of Fujian Department of Science and Technology of ChinaNo.2011Y0027
文摘Evidence suggests that interleukin-10（IL-10） deficiency exacerbates inflammation and worsens the outcome of brain ischemia. In view of the critical role of the single nucleotide polymorphic sites-1082（A/G） and-819（C/T） in the promoter region of the IL-10 gene, we hypothesized that they are associated with cerebral infarction morbidity in the Chinese Han population. We genotyped these allelic gene polymorphisms by amplification refractory mutation system-polymerase chain reaction methods in 181 patients with cerebral infarction（cerebral infarction group） and 115 healthy subjects（control group）. We identified significant differences in genotype distribution and allele frequency of the IL-10-1082 A/G allele between cerebral infarction and control groups（χ2 = 6.643, P = 0.010）. The IL-10-1082 A allele frequency was significantly higher in the cerebral infarction group（92.3%） than in the control group（86.1%）（P = 0.015）. Moreover, cerebral infarction risk of the AA genotype was 2-fold higher than with the AG genotype（OR = 2.031, 95%CI： 1.134-3.637）. In addition, AA genotype together with hypertension was the independent risk factor of cerebral infarction（OR = 2.073, 95%CI： 1.278-3.364）. No statistical difference in genotype distribution or allele frequency of IL-10-819 C/T was found between cerebral infarction and control groups（P 〉 0.05）. These findings suggest that the IL-10-1082 A/G gene polymorphism is involved in cerebral infarction, and increased A allele frequency is closely associated with occurrence of cerebral infarction.
文摘AIM:Phase I/II enzymes metabolize environmental carcinogens and several functional polymorphisms have been reported in their encoding genes. Although their significance with regard to esophageal carcinogenicity has been examined epidemiologically, it remains controversial. The present systematic review of the literature was performed to clarify associations. METHODS: Eligible studies were case-control or cohort studies published until September 2004 that were written in any language. From PubMed and a manual review of reference lists in relevant review articles, we obtained 16 studies related to the CYP1A1 Ile-Val substitution in exon 7, CYP1A1 MspI polymorphisms, CYP2E1 Rsal polymorphisms, GSTM1 null type, GSTT1 null type and GSTP1 Ilel04Val. All were of case-control design. Summary statistics were odds ratios (ORs) comparing heterozygous-, homozygous-non-wild type or these two in combination with the homozygous wild type, or the null type with the non-null type for GSTM1 and GSTT1, A random effect model was used to estimate the summary ORs. A meta-regression analysis was applied to explore sources of heterogeneity. RESULTS: Individuals with the Ile-Val substitution in CYP1A1 exon 7 had increased esophageal cancer risk, with ORs (95%CI) compared with lie/lie of 1.37 (1.09-1.71), 2.52 (1.62-3.91) and 1.44 (1.17-1.78) for Ile-Val, Val/Val genotype and the combined group. No significant association was found between esophageal cancer risk and the other genetic parameters. CONCLUSION: A significant association exists between the CYP1A1 Ile-Val polymorphism and risk of esophageal cancer. Polymorphisms that increase the internal exposure to activated carcinogens may increase the risk of esophageal cancer.
基金supported by the National Natural Science Foundation of China (Nos.30630058 and 30571725)the Xi'an Municipal Science and Technology Research Project Fund (No.GG06152)the Shanxi Provincial Science and Technology Research and Development Project Fund (No.2007K14-01),China
文摘Objective： To investigate the relationships between endothelial nitric oxide synthases （eNOS） G894T and 27 bpvariable number tandem repeat （VNTR） gene polymorphisms and osteoporosis in the postmenopausal women of Chinese Han nationality. Methods： In the present study, 281 postmenopausal women from Xi＇an urban area in West China were recruited, and divided into osteoporosis, osteopenia, and normal groups according to the diagnostic criteria of osteoporosis proposed by World Health Organization （WHO）. The bone mineral density （BMD） values of lumbar vertebrae and left hips were determined by QDR-2000 dual energy X-ray absorptiometry. Blood samples were tested for plasma biochemical indicators including testosterone, estradiol, calcitonin, osteocalcin, and procollagen type I amino-terminal propeptide by enzyme-linked immunosorbent assay （ELISA）, tartrate-resistant acid phosphatase by spectrophotometric method, and the content of nitric oxide by Griess method. Genome DNA was extracted from whole blood, and G894T polymorphism of eNOS gene was analyzed by using polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） method and 27 bp-VNTR polymorphism of eNOS gene was genotyped by PCR method. Then the relationships between genotypes and biochemical indicators, genotypes and osteoporosis, and haplotypes and osteoporosis were analyzed. Results： The average BMD values of the femoral neck, ward＇s triangle and lumbar vertebrae 1-4 （LI-L4） in the subjects with T/T genotype in eNOS G894T locus were significantly higher than those in the subjects with G/T and G/G genotypes （P〈0.05）. The average BMD of the femoral neck in the subjects with a/a genotype of eNOS 27 bp-VNTR locus was evidently higher than that in the subjects with b/b genotype （P〈0.05）. The plasma testosterone and osteocalcin concentrations in the subjects of eNOS G894T G/T genotype were evidently higher than those in the subjects of other genotypes （P〈0.05）; the plasma estradiol concentration in the subjects of eNOS 27 bp-VNTR a/a genotype was obviously higher than that in the subjects of b/b genotype （P〈0.01）. eNOS G/G homozygous frequencies in osteoporosis women, osteopenia women, and normal women were 85.37%, 76.38%, and 83.87%, respectively （P〉0.05）. 0% osteoporosis woman, 0.79% osteopenia women, and 3.23% normal women were eNOS a/a homozygous （P〈0.05）. The frequencies of eNOS 27 bp-VNTR a allele were 5.33% in the osteoporosis group, 10.24% in the osteopenia group, and 16.13% in the normal group （P〈0.05, odds ratio （OR）=0.29, 95% confidence interval （CI）=0.11-0.77）, suggesting that a/a genotype and a allele might have protective effects on osteoporosis. The haplotype analysis showed that G-b was 87.7% （214/244） in the osteoporosis group （P〈0.05, OR=2.48, 95% CI=1. 18-5.18）. G-a was 5.3% （13/244） in the osteoporosis group （P〈0.05, OR=0.29, 95% CI=0. 11-0.77）. G-b was a risk factor for osteoporosis, and G-a a protective factor. Conclusion： eNOS G894T G/T genotype influenced the plasma testosterone and osteocalcin concentrations, and T/T genotype influenced BMD. eNOS 27 bp-VNTR a/a genotype increased plasma estradiol concentration to have a protective effect on osteoporosis.
文摘Latin America shows one of the highest incidence rates of gastric cancer in the world,with variations in mortality rates among nations or even within countries belonging to this region.Gastric cancer is the result of a multifactorial complex process,for which a multistep model of carcinogenesis is currently accepted.Additionally to the infection with Helicobacter pylori,that plays a major role,environmental factors as well as genetic susceptibility factors are significant players at different stages in the gastric cancer process.The differences in population origin,demographic structure,socio-economic development,and the impact of globalization lifestyles experienced in Latin America in the last decades,all together offer opportunities for studying in this context the influence of genetic polymorphisms in the susceptibility to gastric cancer.The aim of this article is to discuss current trends on gastric cancer in Latin American countries and to review the available published information about studies of association of gene polymorphisms involved in gastric cancer susceptibility from this region of the world.A total of 40 genes or genomic regions and69 genetic variants,58%representing markers involved in inflammatory response,have been used in a number of studies in which predominates a low number of individuals(cases and controls)included.Polymorphisms of IL-1B(-511 C/T,14 studies;-31 T/C,10 studies)and IL-1RN(variable number of tandem repeats,17 studies)are the most represented ones in the reviewed studies.Other genetic variants recently evaluated in large metaanalyses and associated with gastric cancer risk were also analyzed in a few studies[e.g.,prostate stem cell antigen(PSCA),CDH1,Survivin].Further and better analysis centered in gene polymorphisms linked to other covariates,epidemiological studies and the information provided by meta-analyses and genome-wide association studies should help to improve our understanding of gastric cancer etiology in order to develop appropriate health programs in Latin America.
基金supported by grants from the National Natural Science Foundation of China(81470893)Zhejiang Provincial Natural Science Foundation of China(LY14H030003)Zhejiang Provincial Medical & Hygienic Science and Technology Project of China(2018KY385)
文摘BACKGROUND:New-onset diabetes after transplantation(NODAT) has become one of the major factors that affect the overall survival and long-term life quality in liver transplantation(LT) recipients. Previous studies found that the serum adiponectin concentration of diabetic patients is significantly lower than that of healthy subjects. Adiponectin regulates the blood glucose level by increasing body sensitivity to insulin through various mechanisms. In this study, we aimed to investigate the impact of diabetes related gene polymorphisms on the development of NODAT in liver recipients.METHODS:A total of 256 LT patients in a single-center were selected retrospectively for the study. Genomic DNA was extracted from explanted liver tissues, and tested for twelve diabetes mellitus associated single nucleotide polymorphisms by Sequenom Mass ARRAY. Modified clinical models in predicting NODAT were established and evaluated.RESULTS:The GG genotype of ADIPOQ rs1501299 gene polymorphism was significantly more frequent in NODAT than non-NODAT LT patients(56% vs 39%, P=0.014). Dominant model(GG vs GT+TT, P=0.030) and recessive model(GT+GG vs TT, P=0.005) also confirmed the genotype distribution difference between NODAT and non-NODAT groups. Age(OR=1.048, P=0.004), BMI(OR=1.107, P=0.041), and blood tacrolimus level at 1-month LT(OR=1.170, P=0.003) were clinical independent risk factors of NODAT. Furthermore, rs1501299 could improve the ability of clinical model in predicting NODAT(AUROC=0.743, P<0.001).CONCLUSION:ADIPOQ rs1501299 gene polymorphism is associated with an increased risk of NODAT, which should be added to the clinical models in predicting the occurrence of NODAT in LT recipients.
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 Department of Biotechnology,Government of India,New Delhi(DBT Project),No.BT/PR 4640/MED/30/716/2012
文摘AIM To investigate the role of genetic variants of angiotensin converting enzyme(ACE) and angiotensinogen(AGT) genes in the antiproteinuric efficacy of ACE inhibitor therapy in diabetic nephropathy(DN) patients.METHODS In the present study, 270 type 2 diabetes mellitus patients with nephropathy were enrolled and treated with ACE inhibitor(ramipril) and followed at 6 mo for renal function and albumin excretion by estimating serum creatinine, end stage renal disease, and albumin/creatinine ratio(ACR) in urine. Genotyping of ACE I/D and AGT M235 T polymorphisms were performed by using primer specific polymerase chain reaction(PCR) and PCR-RFLP techniques, respectively. RESULTS Forty-eight percent of DN patients(responders) benefited with respect to proteinuria from ACE inhibitor therapy at 6 mo follow-up. A significant reduction in ACR was observed after 6 mo treatment with ACE inhibitor irrespective of whether DN patients were micro-albuminuric(≥ 30 and < 300 mg/g creatinine) or macro-albuminuric(≥ 300 mg/g creatinine) at the time of enrollment. However, macro-albuminuric patients(55%) showed better response to therapy. A reduction in urinary ACR was found independent of genotypes of ACE I/D and AGT M235 T polymorphisms although macro-albuminuric patients having TT genotype showed statistically insignificant increased response(72%). CONCLUSION ACE inhibitor therapy reduced urinary ACR by ≥ 30% in 50% of DN patients and the response is independent of ACE I/D and AGT M235 T polymorphisms.
基金supported by the project of Science Fund for Creative Research Groups of the National Natural Science Foundation of China(81221002)Rational Medication Application Patterns of Schizophrenia(BMU20140430) of Peking University Health Science Center
文摘Dear editor, P-glycoprotein （P-gp, also known as ATP-binding cassette transport sub-family B member 1, ABCB1） is a potent ATP-dependent efflux pump for a wide variety of drugs. Although studies of its substrates are abundant [ 1, 2], and ABCB1 is a well-conserved gene, there is increasing evi- dence that its polymorphisms affect substrate specificity [3]. A previous study reported that the synonymous single nucleotide polymorphism （SNP） C3435T （rs1045642） affects the timing of co-translational folding and insertionof P-gp into the membrane,
文摘Objectives Apolipoprotein(Apo) A5 gene poly-morphisms and alcohol consumption have been associated with increased serum triglyceride(TG) levels,but little is known about their interactions on serum lipid levels.The present study was undertaken polymorphismsand alcohol consumption on serum lipid levels.Methods A total of 516 unrelated nondrinkers and 514 drinkers aged 15 -89 were randomly selected from our previous stratified randomized cluster samples.Genotyping of the ApoA5was performed by polymerase chain reaction and restriction fragment length polymorphism,and then confirmed by direct sequencing.Interactions of the ApoA5alcohol consumption were assessed by using a cross-product term between genotypes and the aforementioned factor.Results The levels of total cholesterol (TC),TG,high-density lipoprotein cholesterol(HDL-C), ApoA1 and ApoB were higher in drinkers than in nondrinkers (P【0.05-0.001).The genotypic and allelic frequencies of the three single nucleotide polymorphisms(SNPs) were not different between the two groups.The levels of TG in non-drinkers, and TC,TG,low-density lipoprotein cholesterol (LDL-C)and ApoB in drinkers were different among the three -1131T】C genotypes(P【0.05-0.001).The -1131C allele carriers had higher serum TC,TG,LDL-C and ApoB levels than the allele noncarriers.The levels of TG,HDL-C and ApoB in nondrinkers,and TG and HDL-C in drinkers were different between the two c.553G】T genotypes(P【0.05-0.01).The C.553T allele carriers had higher serum TG and ApoB levels,and lower HDL-C levels than the allele noncarriers.Serum lipid levels in nondrinkers were not different among the three c.457G】A genotypes(P【0.05 for all), but the levels of HDL-C,LDL-C,ApoA1 and ApoB in drinkers were different between the GG and GA/AA geno-types (P【0.05-0.001).The C.457A allele carriers had lower serum HDL-C,LDL-C,ApoAl and ApoB levels than the allele noncarriers.We also observed four haplotypes:G-G-T, G-G-C,G-A-T,and T-G-C with frequencies ranging from 0.06 to 0.87,representing 100%of all haplotypes in the both populations.The ApoA5 haplotypes were significantly(P【0.05) associated at the global level with TC,TG,HDL-C, LDL-C,Apo1,and ApoB,even after correction for multiple testing with permutation test.In particular,carriers of haplo-type G-G-C had significantly higher TC,TG,LDL-C,ApoB than noncarriers,whereas carriers of haplotype C-A-T had significantly lower TC,LDL-C,ApoAl and ApoB,and higher HDL-C than noncarriers.Serum TC levels in nondrinkers were correlated with -1131T】C genotype and allele(P【0.05 for each),whereas serum TC,TG and LDL-C levels in drinkers were associated with -1131 T】C and C.553G】T genotypes,or c.457G】A alleles(P【0.05-0.001).Serum lipid parameters were also correlated with several environmental factors in the both groups.Conclusions The differences in serum lipid profiles between the drinkers and nondrinkers might partly result from different interactions of ApoA5 gene polymor phisms and alcohol consumption.genotypes and -1131T】C, c.553G】T and c.457G】A to detect the interactions of the ApoA5
文摘BACKGROUND:Genetic variations of the 5-lipoxygenase activating protein and leukotriene A4 hydrolase genes that confer an increased risk of ischemic stroke have implicated the family of leukotrienes as potential mediators of ischemic stroke.This study aimed to explore the association of ALOX5,LTA4 H and LTC4 S gene polymorphisms with ischemic stroke risk in a cohort of Chinese in east China.METHODS:This case-control study consisted of 690 patients with ischemic stroke and 690 controls.Polymorphisms of ALOX5 rs2029253 A/G,LTA4 H rs6538697 T/C,and LTC4 S rs730012 A/C were genotyped by the polymerase chain reaction and restriction fragment length polymorphism(PCR-RFLP) analysis.The multivariate logistic regression model was used to exclude the effects of conventional risk factors on ischemic stroke.RESULTS:Carriers of C allele in rs730012 were more susceptible to ischemic stroke(OR:1.37;95%CI:1.08-1.73;P=0.009).The rs2029253 GG genotype showed a risk-reducing effect on ischemic stroke(OR:0.72;95%CI:0.55-0.93;P=0.013) while the rs6538697 CC genotype had an increased risk of ischemic stroke(OR:1.77;95%CI:1.09-2.89;P=0.022).The rs730012 variant was not associated with ischemic stroke risk after adjusting confounding factors(P>0.05).CONCLUSION:The present study suggested that gene polymorphisms in the leukotrienes pathway may exert influences,with independent genetic effects,on ischemic stroke susceptibility in a cohort of Chinese in east China.
基金funded by the National Natural Science Foundation of China,No.81360434
文摘Developmental dyslexia is a complex reading and writing disorder with strong genetic components. In previous genetic studies about dyslexia, a number of candidate genes have been identified. These include DCDC2, which has repeatedly been associated with developmental dyslexia in various European and American populations. However, data regarding this relationship are varied according to population. The Uyghur people of China represent a Eurasian population with an interesting genetic profile. Thus, this group may provide useful information about the association between DCDC2 gene polymorphisms and dyslexia. In the current study, we examined genetic data from 392 Uyghur children aged 8–12 years old from the Xinjiang Uyghur Autonomous Region of China. Participants included 196 children with dyslexia and 196 grade-, age-, and gender-matched controls. DNA was isolated from oral mucosal cell samples and fourteen single nucleotide polymorphisms（rs6456593, rs1419228, rs34647318, rs9467075, rs793862, rs9295619, rs807701, rs807724, rs2274305, rs7765678, rs4599626, rs6922023, rs3765502, and rs1087266） in DCDC2 were screened via the SNPscan method. We compared SNP frequencies in five models（Codominant, Dominant, Recessive, Heterozygote advantage, and Allele） between the two groups by means of the chi-squared test. A single-locus analysis indicated that, with regard to the allele frequency of these polymorphisms, three SNPs（rs807724, rs2274305, and rs4599626） were associated with dyslexia. rs9467075 and rs2274305 displayed significant associations with developmental dyslexia under the dominant model. rs6456593 and rs6922023 were significantly associated with developmental dyslexia under the dominant model and in the heterozygous genotype. Additionally, we discovered that the T-G-C-T of the four-marker haplotype（rs9295619-rs807701-rs807724-rs2274305） and the T-A of the two-marker haplotype（rs3765502-1087266） were significantly different between cases and controls. Thus, we conclude that DCDC2 gene polymorphisms are associated with developmental dyslexia in Chinese Uyghur children.
文摘Coronary heart disease （CHD） is a major health problem in many countries and its pathogenesis is not yet fully understood, contributing to significant morbidity and mortality. Accumulated evidence manifest clearly that CHD is determined by a complex interplay of genetic and environmental factors. Many clinical data have showed that the renin-angiotensin system （RAS） hypertension and CHD involved in many cardiovascular diseases, such as Angiotensinogen （AGT） is the key components of the RAS system, and two gene polymorphisms of AGT had been detected of the CHD risk： M235T and T174M. This article reviews the effects of AGT gene polymorphisms on the CHD.
文摘Objective Coronary heart disease （CHD） is a multifactorial disease. This meta-analysis was performed to evaluate the relationship between angiotensinogen gene polymorphisms and CHD in the Chinese population. Methods We searched literature in pubmed （1990- 2010.8） and CNKI （1990-2010.8） for all the relevant studies on 2 angiotensinogen polymorphisms （M235T and T174M） and risk of CHD. The meta-analysis software Stata 10.0 was used for ascertaining heterogeneity among individual studies and for combining all the studies. Furthermore,Egger＇s test and sensitivity analysis were performed to insure authenticity of the outcome.Results Ten associations studies on 2 angiotensinogen polymorphisms （M235T and T174M） were included in this meta-analysis. In a combined analysis, the summary per-allele odds ratio for CHD of the M235T polymorphism was 1.374 （95% confidence interval, 1.019 to 1.852） and T174M polymorphism was 4.089 （95% confidence interval, 1.697 to 9.851）. Conclusions The M235T polymorphism had weak but statistically significant association with CHD while the T174M polymorphism was more strongly associated with a CHD risk in Chinese population, but further confirmation studies are needed
基金supported by the grants from the National Nature Science Foundation of China(No.U0932603)the Natural Science Foundation of Yunnan Province(No.2009CC001)the Science and Technology Project of Yunnan Provincial Science and Technology Department(No.2011FZ005)
文摘Essential hypertension is one of the most common multi- factorial diseases, affecting 20%--30% of the human popula- tion （Ibrahim and Damasceno, 2012）. Based on the results of twin studies, adoption studies and statistical analyses of blood pressure （BP） across various pedigrees, it has been estimated that 30%--50% of the variability in blood pressure among the general population is genetically determined （Garcia et al., 2003）. Although the genetic mechanisms of essential hyper- tension have not been studied well, investigations for the genes that constitute the renin-angiotensin system （RAS） appear to be particularly promising, since this system plays a central role in the regulation of blood pressure （Ferrario, 2010）.
