目的 探索福建汉族人群TCF7L2基因多态性以及基因-环境交互作用与2型糖尿病(T2DM)的关联性。方法 采用1∶1匹配病例对照研究方法,选取福建省5个国家疾病监测点社区人群中2型糖尿病患者298例和对照者298例,进行问卷调查、体格测量和实验室检测。采用MALDI-TOF-MS技术检测TCF7L2基因的10个SNPs位点(rs11196205、rs12255372、rs4506565、rs7901695、rs7903146、rs7895340、rs11196218、rs12775879、rs290481、rs6585205)的基因型,采用SHEsis在线软件分析基因型分布频率和单体型,应用广义多因子降维法(GMDR)分析基因-环境交互作用,非条件logistic回归模型进行基因-环境交互作用危险性分析, Andersson Excel表计算相加交互作用指标:相对超额危险度比(RERI)、归因比(AP)和交互作用指数(S)。结果 TCF7L2基因10个SNP位点在病例组与对照组之间差异无统计学意义;向心性肥胖为T2DM的主效应影响因素;HOMA-β在病例组rs290481位点的三种基因型中的差异有统计学意义(P<0.05)。结论 向心性肥胖对T2DM起主要影响作用;TCF7L2 基因rs290481多态性可能影响胰岛β细胞胰岛素分泌功能。
Abstract
Objective To explore the association of TCF7L2 gene polymorphisms and gene-environmental interaction with type 2 diabetes mellitus (T2DM.). Methods A 1:1matched case control study was conducted, and 298 cases of T2DM and 298 controls were selected from community population in 5 national disease surveillance points of Fujian province. The questionnaire survey, physical examination and laboratory examination were carried out. The genotypes of 10 SNP loci of TCF7L2 gene (rs11196205, rs12255372, rs4506565, rs7901695, rs7903146, rs7895340, rs11196218, rs12775879, rs290481, rs6585205) were detected by MALDI-TOF-MS. Genotype distribution frequency and haplotype were analyzed by SHEsis online software. Generalized multifactor dimensionality reduction (GMDR) method was used to evaluate gene-environmental interactions. Unconditional logistic regression model was used to analyze the risk of gene-environmental interaction. Andersson Excel table was used to evaluate additive interaction indicators, such as the relative excess risk due to interaction (RERI), the attributable percent (AP), and the interaction index (S). Results There were no significant differences of 10 SNPs distribution of TCF7L2 between the case group and control group.Central obesity is the main effect factor of T2DM. There were significant differences of HOMA-β among the three genotypes of rs290481 in the case group(P<0.05). Conclusion Central obesity played a major role in T2DM in this study. The polymorphism of rs290481 of TCF7L2 gene may affect insulin secretion function of pancreatic islet β cell.
关键词
糖尿病,2型 /
TCF7L2 /
基因多态性 /
环境 /
交互作用
Key words
Diabetes mellitus /
Type 2 /
TCF7L2 /
Gene polymorphism /
Environment /
Interaction
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基金
福建省卫生系统中青年骨干人才培养项目(2013-ZQN-JC-11)
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