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目的:探讨中国2型糖尿病(type 2 diabetes ,T2DM)吸烟人群中腺苷酸活化蛋白激酶α1 (adenosine monophosphate-activated protein kinase α1 subunit,AMPKα1)基因多态性与冠心病(coronary artery disease, CAD)风险的相关性。方法:2014年3月至2019年3月纳入天津市第五中心医院门诊和住院的173名T2DM吸烟患者(其中冠心病126例,无冠心病47例)和231名无吸烟患者(其中冠心病134人,无冠心病97人)作为对照。HapMapCHB数据库选取AMPKα1基因共5个单体型标记的单核苷酸多态性(tag-single nucleotide polymorphisms ,tag-SNPs)(rs249428,rs837103,rs133671707,rs3805489和rs3805486)。应用聚合酶链式反应-限制性内切酶片断长度多态性方法(polymerase chain reaction-restriction fragment length polymorphism ,PCR-RFLP)检测AMPKα1基因tag-SNPs基因型和基因频率,分析T2DM吸烟人群AMPKα1基因多态性与CAD的关系。结果:①吸烟患者中冠心病组和非冠心病组AMPKα1等位基因频率比较:rs249428,rs837103,rs133671707,rs3805489和rs3805486等位基因频率之比分别为54%比57.4%,69.0%比68.1%,22.2%比29.8%,63.5%比36.2%,50.8%比55.3%。rs3805489基因与冠心病发病风险差异有统计学意义(n P=0.005)。且rs3805489等位基因C携带者较A携带者发生冠心病的风险下降(n OR值为0.450,95%n CI为0.271~0.749,n P=0.003),且其基因型频率在两组间的分布差异有统计学意义(n P=0.005),在校正其他已知的冠心病风险因素后,差异仍有统计学意义(n P′=0.032)。C/C或A/C基因型携带者与A/A者相比,冠心病风险下降(n OR值为0.360,95%n CI′-为0.167~0.774,n P′-=0.009)。②在非吸烟患者中,AMPKα1各SNPs等位基因和基因型分布频率在冠心病组和非冠心病组之间差异均无统计学意义(n P>0.05)。n 结论:T2DM吸烟患者中,rs3805489基因与冠心病发病风险相关,提示AMPKα1基因变异可能是中国吸烟T2DM患者冠心病风险的主要决定因素。“,”Objective:To investigate the association between adenosine monophosphate activated protein α 1 (AMPK α 1) gene polymorphism and coronary heart disease (CAD) risk in Chinese type 2 diabetes (T2DM) smokers .Methods:All patients were from the outpatient or inpatient the Fith Central Hospital of Tianjin from March 2014 to March 2019, 173 smokers with T2DM(126 individuals with CAD as cases and 47 non-CAD as controls )and 231 no smoker with T2DM (134 individuals with CAD as cases and 97 non-CAD as controls )were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.Five haplotype-tagging single nucleotide polymorphisms (SNPs) in AMPKα1 gene were selected from HapMap database (rs249428, rs837103, rs133671707, rs3805489 and rs3805486). The relationship between AMPK α 1 gene polymorphism and CAD in T2DM smokers were compared.Results:①Comparison of AMPK α 1 allele frequency between CAD group and non CAD group in smoking patients: The allele frequencies of rs249428, rs837103, rs133671707, rs 3805489 and rs3805486 were 54% vs 57.4%, 69.0% vs 68.1%, 22.2% vs 29.8%, 63.5% vs 36.2% and 50.8% vs 55.3%, respectively, there was significant difference between rs3805489 gene and coronary heart disease risk ( n P=0.005). The risk of CAD (n OR=0.450, 95%n CI=0.271~0.749, n P=0.003) was lower in rs 3805489 allele C carriers than in a carriers, and the distribution difference of genotype frequency between the two groups was statistically significant (n P=0.005). After adjusting other known risk factors of CAD, the difference was still statistically significant (n P′=0.032). The risk of CAD in C/C or A/C genotype carriers was lower than that in A/A (n OR=0.360, 95% n CI=0.167~0.774, n P′=0.009). ②In no smoking type 2 diabetes , there was no statistical difference in the distribution of allele frequencies between the CAD and non-CAD group in AMPKα1 gene (n P>0.05).n Conclusion:Rs3805489 gene is related to the risk of CAD in T2DM smokers, AMPK α 1 gene polymorphism may be the main determinant of CAD risk in T2DM smokers in China.