福建汉族人群TCF7L2基因多态性、机体及环境因素与2型糖尿病关联性研究

发布时间：2018-05-23 23:42

本文选题：2型糖尿病 + 病例对照研究　；参考：《福建医科大学》2015年硕士论文

【摘要】：目的探讨TCF7L2基因多态性与2型糖尿病(type 2 diabetes,T2DM)的关联性,筛选T2DM的环境影响因素及机体因素,探讨TCF7L2基因多态与机体及环境因素之间交互作用对T2DM的影响。研究方法采用1:1病例对照研究方法,选择福建省的5个国家疾病监测点的社区人群中T2DM患者为病例,选择与病例同性别、同居住地、同民族、年龄相差小于5岁的非糖尿病的人群为对照。对进入研究的596名对象进行环境因素的调查,体格测量和血清学指标的检测,并提取血样DNA,应用Mass ARRAY技术检测TCF7L2基因上的10个SNPs位点(rs11196205、rs12255372、rs4506565、rs7901695、rs7903146、rs7895340、rs11196218、rs12775879、rs290481、rs6585205)的基因型。采用Epidate3.1软件建立数据库,SHEsis软件分析基因型及单体型。GMDR.09软件分析构建TCF7L2基因各SNP位点、基因-环境及机体因素交互作用模型,其余统计分析采用SPSS 18.0软件。研究结果共有596名研究对象参加了研究,T2DM病例和对照各298例,婚姻、教育程度在两组间的分布没有统计学差异。1.TCF7L2基因多态与T2DM的关系TCF7L2基因各SNP位点的基因型分布均符合Hardy-Weinberg遗传平衡检验;尚未发现TCF7L2基因各SNP位点与T2DM相关;尚未发现TCF7L2基因各SNP位点构建的单体型与T2DM相关。2.血清学、体格测量指标与T2DM的关系Hs-CRP、TC、HDL-C、TG、Hb A1c、SBP、DBP、BMI、WC各指标检测水平病例组均显著高于对照组(P0.050),与T2DM密切相关。3.T2DM的危险因素筛选出T2DM的危险因素有:吸烟(OR=1.702,OR95%CI=1.029-2.813),饮酒(OR=1.963,OR95%CI=1.246-3.093),向心性肥胖(OR=2.348,OR95%CI=1.591-3.465),高血压疾病史(OR=2.219,OR95%CI=1.379-3.288)和血脂异常疾病史(OR=2.730,OR95%CI=1.323-5.633);保护因素为是食用新鲜水果(OR=0.679,OR95%CI=0.297-0.969)。4.TCF7L2基因、机体及环境因素交互作用与T2DM的关系向心性肥胖对T2DM的影响为主效应因素;向心性肥胖与吸烟存在负相加交互作用;病例组HOMA-β在rs290481位点的三种基因分型中均具有统计学意义。结论5.1本次研究尚未发现TCF7L2基因10个SNPs多态性与T2DM相关;尚未发现TCF7L2基因的10个SNPs构建的单体型与T2DM存在关联;5.2本次研究发现吸烟、饮酒、向心性肥胖、高血压疾病史、高血脂疾病史是福建汉族人群T2DM的危险因素,食用新鲜水果是保护因素;5.3向心性肥胖在TCF7L2基因、机体及环境因素对T2DM的影响中起主要作用;5.4 TCF7L2基因rs290481多态可能影响胰岛素的分泌。
[Abstract]:Objective to investigate the association between TCF7L2 gene polymorphism and type 2 diabetes mellitus (T2DM), to screen the environmental and body factors of T2DM, and to explore the effect of TCF7L2 gene polymorphism on T2DM. Methods the 1:1 case-control study was used to select the T2DM patients in the community population of five national disease surveillance sites in Fujian Province, and choose the same sex, same place of residence, same nationality as the case. Non-diabetic subjects with age differences of less than 5 years were controls. A total of 596 subjects were investigated for environmental factors, physical measurements and serological indices, and blood DNA samples were extracted. The genotypes of 10 SNPs loci rs12255372rs4506565rs79031465rs79031465rs11196218rs127758791rs290481rs6585205 were detected by Mass ARRAY technique. The TCF7L2 gene SNP loci, gene-environment and organism interaction models were constructed by using Epidate3.1 software to establish a database for genotype analysis and haplotype. GMDR.09 software was used to analyze the genotype and haplotype. The other statistical analysis software was SPSS 18.0. The results showed that a total of 596 subjects took part in the study of T2DM cases and 298 controls each. There was no statistical difference in the distribution of educational level between the two groups. 1. The relationship between the polymorphism of TCF7L2 gene and T2DM the genotype distribution of SNP loci of TCF7L2 gene all accord with the Hardy-Weinberg genetic balance test, the SNP loci of TCF7L2 gene were not found to be associated with T2DM. Haplotypes constructed at SNP sites of TCF7L2 gene have not been found to be related to T2DM. Serology, The relationship between physical parameters and T2DM: Hs-CRPU TCU HDL-Cn TGG HbA1cBMI-WC level was significantly higher than that of control group P0.0500.The risk factors of T2DM closely related to T2DM were as follows: smoking OR1.702OR95CI1.02.813C, alcohol drinking OR1.963OR95CIT 1.246-3.093C, heart obesity OR2.348OR9595 CIQ 1.591-3.4655.The risk factors of T2DM were as follows: smoking OR1.702OR95CI1.02.2.963CIT 1.246-3.093C, and heart obesity OR2.348OR9595. The risk factors of T2DM were 1.591-3.4650.The risk factors of T2DM were as follows: smoking OR1.702O95CI1.02.8130.The alcohol drinking OR1.963OR95CII was 1.246-3.093C, and the risk factors were 1.591-3.465. The disease history is 2.219 / OR95CIN 1.379-3.288) and the history of dyslipidemia is 2.730 / OR95CIQ 1.323-5.633. The protective factors are the consumption of fresh fruit OR0.679, OR95CIN 0.297-0.969C, and 4.TCF7L2 gene. The relationship between the interaction of body and environment factors and T2DM; the negative additive interaction between concentric obesity and smoking; and the significant difference of HOMA- 尾 in the three genotypes of rs290481 locus. Conclusion in this study, 10 SNPs polymorphisms of TCF7L2 gene were not found to be associated with T2DM, and haplotypes constructed by 10 SNPs of TCF7L2 gene were not found to be associated with T2DM. The history of hyperlipidemia is a risk factor for T2DM in Fujian Han population, and eating fresh fruit is a protective factor in TCF7L2 gene. The effect of body and environment factors on T2DM may play a major role in the effect of rs290481 polymorphism of TCF7L2 gene on insulin secretion.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.1

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