中国2型糖尿病人群AMPKα2基因多态性与冠心病风险的相关性研究  

Genetic variability in AMPKα2 gene is associated with risk of coronary artery disease in Chinese type 2 diabetics

作　　者：马晓伟[1] 邓瑞芬[1] 丁钐[1] 顾楠[1] 马晓丹[1] 李建平[2] 郭晓蕙[1] 

机构地区：[1]北京大学第一医院内分泌科,100034 [2]北京大学第一医院心血管内科,100034

出　　处：《中国糖尿病杂志》2011年第12期881-886,共6页Chinese Journal of Diabetes

基　　金：国家973计划课题资助项目(2006CB503903;2006CB503908)

摘　　要：目的研究我国T2DM人群AMPKα2基因多态性与冠心病(CAD)风险的相关性。方法以326例T2DM患者为研究对象,其中180例伴有CAD(CAD+组),146例不伴CAD(CAD组)。应用聚合酶链式反应—限制性内切酶片断长度多态性(PCR-RFLP)技术或基因测序方法 ,研究AMPKα2基因8个单倍型标记单核苷酸多态性(tag-SNPs)与CAD风险的关系。结果 (1)SNP rs11206887 GG基因型携带者较非携带者发生CAD的风险显著增加(OR=2.507,95%CI=1.244～5.053,P=0.010),校正年龄、性别、BMI、吸烟、糖尿病病程后仍存在统计学差异(OR'=2.469,95%CI'=1.182～5.157,P'=0.016)。(2)SNP rs2143749 GG基因型携带者较非携带者发生CAD的风险增高(OR=1.680,95%CI=1.029～2.741,P=0.038)。(3)SNP rs2746347 TT基因型携带者较非携带者发生CAD的风险有增高趋势(OR=2.875,95%CI=1.034～7.996,P=0.043,校正OR'=1.715,95%CI'=1.016～2.895,P'=0.044)。(4)SNP rs2143749和SNP rs11206887 GG/GG基因型组合携带者较非携带者发生CAD的风险增高(P=0.014)。结论我国T2DM患者AMPKα2 SNPs与CAD的发病风险可能相关。Objective To study whether or not the genetic variability in AMPKα2 gene affects the risk of cardiovascular disease in type 2 diabetics. Methods We selected 8 haplotype-tagging single nucleotide polymorphisms （tag-SNPs） at AMPKα2 locus according to the CHB database from HapMap phase Ⅱ （r^2〈 d0. 8 and MAF≥0. 05, R^# 27）, and genotyped 326 unrelated Han subjects with type 2 diabetes （180 CAD-positive and 146 CAD-negative individuals）using the polymerase chain reaction - restriction fragment length polymorphism （PCR-RFLP） assay or directly DNA-sequencing. For each SNP, the odds ratios （ORs） were estimated for CAD as comparing with the CAD-negative individuals by logistic regression analysis （SPSS version 16.0）. Results The carriers of genotype GG at rs11206887 had a higher CAD risk as compared with non-carriers （OR= 2. 507, 95 %CI= 1. 244-5. 053, P： 0. 010）. After adjusting for sex, age, BMI, smoking status and diabetic duration, the difference was still statistically significant （OR′ = 2. 469, 95% CI′ = 1. 182-5. 157, P′ = 0. 016） . GG homozygotes at rs2143749 were found at the increased risk of CAD compared to CC/CG carriers （OR= 1, 680, 95%CI= 1. 029-2. 741, P = 0. 038）. TT homozygotes at rs2746347 had a higher risk of CAD with statistical boundary （OR′= 1. 715, 95%CI= 1. 016-2. 895, P′=0. 044） compared to non-carriers after adjustment. Meanwhile, genotypic combination of SNPs rs2143749 and rs11206887 were associated with the risk of CAD in type 2 diabetic patients, with the carriers of GG/GG at the increased risk of CAD（adjusted ORr= 2. 380,95%CI 1. 136-4. 99, P′= 0. 022）. Conclusion Our findings suggest that genetic variability at AMPKα2 locus may be associated with the risk of CAD in type 2 diabetes in the Chinese population.

关 键 词：AMPKα2基因 单核苷酸多态性 病例对照研究 冠心病 糖尿病 2型 

分 类 号：R541.4[医药卫生—心血管疾病]