中文摘要：

目的分析中国北京地区汉族人群过氧化物酶体增殖物激活受体辅激活因子1α（promoterofperoxisome proliferators—activated receptor-γ coactivator 1α，PPARGC1A）基因启动子中的变异位点分布，并探讨其与2型糖尿病（type2diabetes，T2DM）的关联。方法应用二步法，首先基于小群体（n=216，104例T2DM患者和112名糖耐量正常对照者），通过Sanger法测序扫描识别PPARGCIA基因启动子变异；然后应用聚合酶链式反应-限制性片段长度多态性技术，在更大人群样本进行验证（n=1546，732例T2DM患者和814名糖耐量正常对照者）。所有受试者均测定空腹血糖、胰岛素、血脂、身高、体重、腰围、血压。通过Logistic回归进行关联分析，Haploview软件计算连锁不平衡和单倍型分析。结果Sanger法测序分型筛查共识别5个多态性位点，根据杂合度最终纳入-2120T／C（rs3755857），-1999C／G（rs2946386）和-1437T／C（rs2970870）位点进行基因分型。3个位点的次要等位基因在T2DM患者组和对照组间分布的差异无统计学意义。基于Mantel—Haenszel固定效应模型合并两个群体的OR值，调整年龄和性别因素，发现-1999C／G（rs2946386）的C等位基因增加T2DM的风险1．18倍（P=0．03，OR=1．18）。Permutation校正后，未发现3个位点构建的单倍型与T2DM存在显著关联。结论PPARGC1A基因启动子中-1999C／G（rs2946386）多态性的C等位基因与T2DM风险存在微效关联，PPARGC1A启动子突变可能不是T2DM发生的主要危险因素。

英文摘要：

Objective To study the baseline distribution of polymorphisms in the promoter of peroxisome proliferators-activated receptor-γ coactivator let （PPARGC1A）gene in ethnic Hans from Beijing, and to assess their association with type 2 diabetes （T2DM）. Methods A 2-stage study was designed. Firstly, the promoter region of PPAGC1A gene was screened with PCR-RFLP in a small population （n = 216, T2DM/control： 104/112）, which was followed by a replication study of a larger group （n= 1546, T2DM/control： 732/814）. Fasting plasma glucose, insulin, blood lipid, height, weight, waist circumference, and blood pressure were measured in all subjects. Potential association was assessed by logistic regression. Linkage disequilibrium and baplotype analysis were conducted with Haploview software. Results Five polymorphisms were identified with Sanger sequencing, among which T- 2120C （rs3755857）, - 1999C/G （rs2946386） and - 1437T/C （rs2970870） were included for genotypic analysis based on their moderate levels of heterozygosity. No significant difference was found between the two groups. When adjusted for age and gender confounding, we have combined the OR values from population 1 and population 2 based on Mantel-Haenszel fixed model, and recognized a mild contribution of C allele of - 1999C/G （rs2946386） to the 1.18-fold risk of T2DM （P=0.03, OR=1. 18）. No haplotype was associated with T 2 DM after permutation correction . Conclusion The C allele of -1999C/G （rs2946386） in the promoter region of the PPARGCIA gene is mildly associated with T2DM. Variations in the promoter region of the PPARGCIA gene seem not to confer the risk of T2DM in our population.