中国2型糖尿病人群脂联素受体1基因多态性与冠心病风险的相关性研究

Genetic variability in adiponectin receptor 1 (AdipoR1) is associated with the risk of coronary artery disease in type 2 diabetes in Chinese population

目的研究我国2型糖尿病(T2DM)人群脂联素受体1(AdipoR1)基因多态性与冠心病(CAD)风险的相关性。方法以307例T2DM患者为研究人群,其中205例伴有CAD,102例不伴CAD。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AdipoR1 10个单倍型标记单核苷酸多态性(Haplotype-tagging SNPs)与CAD风险的关系。结果 (1)AdipoR1SNP rs1342387 GG和AG基因型携带者均较AA型携带者发生CAD的风险显著增加(GG vsAA:校正OR′=2.491,95%CI′1.354～6.885,P′=0.031;AG vs AA:校正OR′=3.053,95%CI′1.085～5.718,P′=0.007)。(2)SNP rs12045862基因型CC携带者与TT携带者相比,CAD的风险显著增加(校正OR′=2.751,95%CI′1.063～7.115,P′=0.037)。(3)SNPs rs1342387、rs12045862 GX/CC基因型组合携带者较非携带者CAD的风险显著增加(校正OR′=3.646,95%CI′1.253～10.608,P′=0.018)。保护性基因型组合AA/TX携带者较非携带者发生CAD的风险显著降低(校正OR′=0.260,95%CI′0.113～0.601,P′=0.002)。(4)在超重和肥胖(BMI≥24)的T2DM人群中,发现肥胖与SNPs rs1342387、rs12045862对CAD的风险有相互作用(P<0.05);在总人群中发现的与CAD风险相关的SNPs rs1342387和rs12045862在这一亚组仍具有相关性;同时发现SNP rs7539542基因型CC携带者较GG携带者CAD的风险增加(g正OR′=4.714,P′=0.036)。结论中国T2DM人群中,AdipoR1 SNPs与CAD的风险可能相关。在超重或肥胖T2DM人群中,AdipoR1 SNPs与肥胖对CAD风险的影响有协同作用。

Objective To investigate whether adiponectin receptor 1 gene （AdipoR1） polymorphisms were associated with the risk of coronary artery disease （CAD） in type 2 diabetic patients in China. Methods Of total 307 individuals with type 2 diabetes, 205 with CAD as cases and 102 without CAD as controls were recruited. The PCR-RFLP assay or directly DNA sequencing was adopted to genotype all the subjects for a total of 10 haplotype-tagging single nucleotide polymorphisms （SNPs） in AdipoR1 gene. The frequencies of genotypes and alleles at each SNP were compared between the case and control groups. Results （1） At SNP rs1342387, GG homozygotes had a higher risk for CAD compared to AA homozygotes in type 2 diabetics （OR= 2. 245, 95%CI： 1. 113-4. 530,P=0. 024; OR＇=2. 491, 95%CI 1. 354-6. 885,P＇ =0. 031, after adjusted for other known CAD risk factors）, and the carriers of genotype AG had the increased risk of CAD compared to those of genotype AA（adjusted OR＇： 3. 053, 95%CI 1. 085-5. 718,P＇= 0. 007）. （2）At SNP rs12045862, CC homozygotes had a higher risk for CAD compared to TT homozygotes （adjusted OR＇= 2. 751,95%r 1. 063-7. 115, p＇ = 0. 037）. （3） Genotypic combinations of SNPs rs1342387 and rs12045862 were associated with the risk for CAD in type 2 diabetic patients. GX/CC was associated with the increased risk for CAD（adjusted OR＇= 3. 646,95% CI 1. 253- 10. 608,P＇= 0. 018）. AA/TX provided protection from CAD in type 2 diabetic patients （adjusted OR＇= 0. 260,95% CI 0. 113-0. 601, p＇= 0. 002）. （4） In overweight or obese （BMI≥24） type 2 diabetics, rs1342387 and rs12045862 showed significant interaction with obesity in relation to CAD risk （P for interaction~ 0.05） ; the associated rs1342387 and rs12045862 found in the general type 2 diabetics were consistent in association with CAD risk in the subgroup（P〈0. 05） ; genotype CC at rs7539542 was found to associate with increased CAD risk compared to genotype GG（OR＇=4. 714 ,P＇=0. 036）in the subgroup. Conclusions Genetic variations in AdipoR1 are associated with the risk of coronary artery disease, and interact with obesity on CAD risk in type 2 diabetes in Chinese population.