TCF7L2 rs7903146 polymorphism is associated with gastric cancer: a case-control study in the Venezuelan population

AIM: To explore the association between TCF7L2 rs12255372 and rs7903146 single nucleotide polymorphisms(SNPs) and gastric cancer risk in Venezuelan patients.METHODS: We performed a case-control study including 122 paraffin-embedded archived intestinaltype gastric cancer samples and 129 biopsies obtained by superior endoscopy from chronic gastritis patients. Gastric cancer samples were classified according the degree of carcinoma differentiation. Genomic DNA was extracted from tissues, and the two SNPs of TCF7L2 gene(rs12255372 and rs7903146) were genotyped by polymerase chain reaction-restriction fragment length polymorphism reactions. Multiple regression analysis with adjustments for age and gender were performed and best-fitting models of inheritance were determined.RESULTS: After adjusting for age and sex the TCF7L2 rs7903146 TT genotype was associated with gastric cancer risk under the recessive genetic model(OR = 3.11, 95%CI: 1.22-7.92, P = 0.017). We further investigated the distribution of rs12255372 and rs7903146 genotypes according gastric cancer stratified by degree of differentiation, and we observed that carriers of rs7903146 T allele(CT + TT vs CC) had a significantly increased risk of moderate/well differentiated gastric cancer(dominant model, OR = 2.55, 95%CI: 1.35-4.80, P = 0.004), whereas the rs7903146 TT genotype was associated with poorly differentiated gastric cancer in the recessive model(OR = 3.65, 95%CI: 1.25-10.62, P = 0.018). We did not find association between rs12255372 SNP and the susceptibility of developing gastric cancer. CONCLUSION: TCF7L2 rs7903146 polymorphism is associated with gastric cancer risk in the Venezuelan population, and could be related to determine the degree of differentiation of tumor cells.     

TCF7L2基因单核苷酸多态性与汉族2型糖尿病遗传易感性关系的研究

目的探讨TCF7L2基因单核苷酸多态性与汉族人2型糖尿病遗传易感性的关系。方法无血缘关系江苏地区汉族人1535例,分为2型糖尿病组（T2DM）、糖耐量减低组（IGT）和正常糖耐量组（NGT）,LDR法检测TCF7L2基因rs7903146（C／T）及rs12255372（G／T）单核苷酸多态性。结果（1）T2DM、IGT组rs7903146位点T等位基因频率均高于NGT组,但差异无统计学意义;（2）糖代谢异常组rs7903146位点CT基因型频率及T等位基因频率则显著高于NGT组（P均〈0．05）,T等位基因参与糖代谢异常发生的相对风险为1．589,人群归因危险度为2．1％。结论TCF7L2基因单核苷酸多态分布存在明显的种族异质性,rs7903146位点T突变可能是中国汉族人群糖代谢异常发生的遗传因素之一。     

Association of TCF7L2 rs7903146 Gene Polymorphism with the Risk of NAFLD and CAD in the Chinese Han Population

Background and Aims: Coronary artery disease (CAD) is a major cause of morbidity and mortality in patients with non-alcoholic fatty liver disease (NAFLD). Previous studies have suggested that TCF7L2 rs7903146 was related to the risk of developing NAFLD but the conclusions are not consistent and no related study has been conducted in Chinese populations. The aim of this study was to investigate the association between TCF7L2 rs7903146 and the risk of developing NAFLD and CAD in a Chinese Han population.Methods: TCF7L2 rs7903146 genotypes were measured by the MALDI-TOF-MS from 143 NAFLD patients, 159 CAD patients, 131 NAFLD + CAD patients, and 212 healthy controls. The demographic data and serum lipid profiles of all subjects were collected. The distributions of genotype and allele frequency in each group were also tested. Logistic regression was used to investigate the risk of TCF7L2 rs7903146 with NAFLD and CAD. All statistical analyses were conducted using SPSS 23.0.Results: There were no significant differences in the distributions of TCF7L2 rs7903146 genotype and allele frequency in each of the two groups, and the TCF7L2 rs7903146 CT + TT genotype did not increase the risk of developing NAFLD, CAD, and NAFLD + CAD. Except for body mass index in the control group, the differences of clinical parameters between the TCF7L2 rs7903146 T allele carriers and non-carriers in each group were not significant. In the non-obese group, the TCF7L2 rs7903146 CT + TT genotype was a protective factor for the development of NAFLD in the non-obese subjects (odds ratio=0.359, 95% confidence interval: 0.134-0.961, p = 0.041).Conclusions: TCF7L2 rs7903146 was not associated with the risk of developing NAFLD, CAD, and NAFLD + CAD in the Chinese Han population. In the non-obese population, the TCF7L2 rs7903146 CT + TT genotype was a protective factor against the development of NAFLD.     

TCF7L2基因单核苷酸多态性与妊娠期糖尿病的相关性研究

目的 探讨转录因子7类似物2(TCF7L2)基因rs290487、rs11196205、rs11196218位点单核苷酸多态性(SNP)与妊娠期糖尿病(GDM)的关系.方法 采用病例对照研究方法,选取中国北方地区无血缘关系的糖耐量受损(IGT)孕妇158例、GDM孕妇335例作为病例组,正常妊娠妇女647例作为对照组.提取所有受试者基因组DNA,用连接酶检测反应(LDR)分析TCF7L2基因rs290487、rs11196205、rs11196218位点基因型,并进行相关分析.结果 在rs290487位点,C等位基因频率在病例组为41.6%,明显高于对照组的36.3%(P=0.012).病例组中CC基因型频率为18.7%,明显高于对照组的14.0%(P=0.033).CC基因型GDM发病风险与CT+TT基因型相比,比数比(OR)为1.418(95%CI 1.028～1.955),经logistic回归校正混杂因素后,OR值为1.518(95%CI 1.064～2.166).结论 TCF7L2基因rs290487位点SNP可能在GDM遗传易感性中起重要作用,CC基因型可能是其发生的危险因素.

Abstract：

Objective To investigate the relationship between gene polymorphism of transcripion factor 7-like 2 (TCF7L2) at positions rs290487, rs11196205, rs11196218 and gestational diabetes mellitus (GDM) in Chinese women.Methods In 1140 unrelated pregnant Northern Chinese women (335 women with GDM, 158 gestational cases with impaired glucose tolerance and 647 pregnant non-diabetic controls) ,three single nucleotide polymorphisms (rs290487, rs11196205, and rs11196218) in the TCF7L2 gene were genotyped using ligase detection reaction (LDR).In the present study, cases with GDM and impaired glucose tolerance (IGT) were indistinguishable clinically and biochemically, and were combined into case group.Results The frequency of C allele of rs290487 was 41.6% in case group, being significantly higher than that in control group (36.3%, P=0.012).There was significant difference in the frequency of CC genotype between case group and control group (18.7% vs 14.0%, P=0.033).Compared with T allele carriers, CC genotype carriers had a 1.418-fold increased risk of GDM (95% CI 1.028-1.955).After adjusting for age, body mass index, family history of diabetes,systolic blood pressure,and diastolic blood pressure, pregnant women with CC genotype carriers of rs290487 were more prone to hyperglycemia compared with the T allele carriers (OR 1.518, 95% CI 1.064-2.166).Conclusions The TCF7L2 rs290487 variant may contribute to the genetic predisposition to GDM.CC genotype is likely to be associated with an increased risk of GDM in the pregnant Chinese women.     

TCF7L2多态性与2型糖尿病关系的研究进展

2型糖尿病是一种多基因遗传病,多个微效基因的累加作用造成携带致病基因个体对糖尿病的遗传易感性。转录因子7类似物2（TCF7L2）是继过氧化物酶体增殖物激活受体扎KCNJ11等之后被确认的又一个2型糖尿病易感基因,其危险等位基因是迄今发现的与2型糖尿病的发生关联最强的变异,常见危险位点为rs7903146和rs12255372。TCF7L2属于核受体家族,间接介导Wnt信号传导通路。TCF7L2变异个体的表型为糖刺激后胰岛素分泌不足,但其增加2型糖尿病发病风险的机制尚未明确。