·糖尿病分子生物学与遗传学·

　　马晓伟、邓瑞芬、丁钐、顾楠、马晓丹、郭晓蕙 、李建平

　　作者单位：100034北京大学第一医院内分泌科

　　【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AMPK α2 SNPs与CAD的发病风险可能相关。

　　【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

　　doi:10.3969/j.issn.1006-6187.2011.12.001

　　Genetic variability in AMPKα2 gene is associated with risk of coronary artery disease in Chinese type 2 diabeticsMA Xiao-wei, DENG Rui-fen, DING Shan,et al. Peking University First Hospital, Beijing 100034, China

　　【Abstract】 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 (r2<0.8 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 OR′=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.

　　【Key words】AMP-activated protein kinase subunit α2 (AMPKα2) gene; Single nucleotide polymorphisms; Coronary artery disease (CAD); Diabetes mellitus, type 2