汉族人群ADIPOR1 rs7539542与冠状动脉粥样硬化性心脏病和2型糖尿病的关联分析  

The relationship between ADIPOR1 rs7539542 and the susceptibility of coronary artery disease and type 2 diabetes in Han population

作　　者：李响[1] 蒲连美[1] 阮杨 李红[1] 金泽宁 Li Xiang;Pu Lianmei;Ruan Yang;Li Hong;Jin Zening(Emergency&Critical Care Center,Beijing Anzhen Hospital,Capital Medical University,Beijing 100029,China;Department of Cardiology,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China)

机构地区：[1]首都医科大学附属北京安贞医院急诊危重症中心,北京100029 [2]首都医科大学附属北京天坛医院心内科,北京100070

出　　处：《首都医科大学学报》2020年第6期935-942,共8页Journal of Capital Medical University

基　　金：国家自然科学基金(81570323);心血管疾病精准医学北京实验室(PXM2020_014226_000017_00377132_FCG)。

摘　　要：目的分析ADIPOR1非内含子区域的单核苷酸多态性位点(single nucleotide polymorphisms,SNPs)是否增加冠状动脉粥样硬化性心脏病(以下简称冠心病)和2型糖尿病的易感风险。方法采用多病例-对照设计,选取737例行冠状动脉造影术,以及年龄、性别及体质量指数相匹配的研究对象:193例对照者(对照组)、142例2型糖尿病患者、203例冠心病患者及199例冠心病合并2型糖尿病患者。采用Sanger法对3个SNPs[位于3′非翻译区(untranslated regions,UTR):rs7539542 G>C和rs10581 C>T;位于5′UTR:rs7517286 T>C]进行直接测序。结果rs7539542 C等位基因不仅与冠心病(OR=1.67~2.34,P=2.87×10^-4~0.002)、冠心病合并2型糖尿病(OR=1.52~2.08,P=0.003~0.016)的易感性相关,还增加2型糖尿病患者冠心病的易感风险(OR=1.58~2.90,P=0.002~0.038)。通过对血压进行亚组分析,发现上述关联仅分布于非高血压亚组。进一步在非高血压亚组进行基因与环境的交互作用分析,发现rs7539542 CC基因型与三酰甘油存在交互作用并增加冠心病(P=0.041,OR=5.006)和冠心病合并2型糖尿病(OR=5.381,P=0.04)易感风险。rs7517286和rs10581与冠心病或2型糖尿病的易感性无明显关联(P>0.05)。结论位于ADIPOR 3′UTR的rs7539542多态性位点与冠心病的易感性独立相关,尤其对于非高血压患者。Objective To analyze whether single nucleotide polymorphisms(SNPs)in non-intronic regions contributed to coronary artery disease(CAD)or type 2 diabetes(T2 D)risk.Methods Seven hundred thirty-seven subjects who had undergone coronary arteriography were included in this multi-disease comparative study,with gender-,age-,and body mass index-matched among groups.There were 193 controls,142 patients with T2 D,203 with CAD,and 199 with T2 D and CAD.Three SNPs(rs7539542 G>C and rs10581 C>T at 3′untranslated regions(UTR),rs7517286 T>C at 5′UTR)were genotyped by direct Sanger sequencing.Results rs7539542 C allele was positively associated with both CAD(OR=1.67-2.34,P=2.87×10^-4-0.002)and CAD with T2 D(OR=1.52-2.08,P=0.003-0.016).Further analysis of case-case comparative results showed that rs7539542 C allele was associated with an increased risk of CAD in T2 D patients(OR=1.58-2.90,P=0.002-0.038).Subgroup analyses of blood pressure level suggested that the above associations could only be found in the non-hypertension subgroup.For gene-environment interactions in the non-hypertension subgroup,rs7539542 CC genotype correlated with triglyceride level and contributed to a higher risk of CAD(OR=5.006,P=0.041)and CAD with T2 D(OR=5.381,P=0.04).No significant association was found between rs7517286 or rs10581 variant and CAD or T2 D(P>0.05).Conclusion Our results suggest that rs7539542 at 3′UTR of ADIPOR1 is associated with CAD independently,especially in non-hypertension subjects.

关 键 词：脂联素受体1 rs7539542 冠状动脉粥样硬化性心脏病 2型糖尿病 关联 

分 类 号：R541[医药卫生—心血管疾病] R587[医药卫生—内科学]