ABCA1基因启动子区-191G/C单核苷酸多态性在冠心病中的意义

Significance of -191G/C single nucleotide polymorphisms in the promoter region of ATP-binding cassette transporter gene in coronary artery disease

目的研究ABCA1基因启动子区-191G/C单核苷酸多态性(SNP)对血脂的影响及其在冠心病中的意义。方法用聚合酶链反应-限制性片段长度多态性法(PCR-RFLP)探讨204例冠心病患者和114例正常人的ABCA1基因启动子区-191位点G/CSNP在两组间、冠心病组不同临床表现型之间分布的差异及3种等位基因型与冠心病相关临床指标的关系。结果冠心病组与正常人组比较,3种等位基因型GG、GC、CC分布频率差异具有显著性,CC基因型在冠心病组中的分布频率明显高于正常人组(P<0.05),C等位基因在冠心病组中的分布频率明显高于正常人组(P<0.01)。在稳定性心绞痛组(SAP)和急性冠脉综合征组(ACS),3种等位基因型GG、GC、CC分布频率差异也具有显著性,ACS组CC基因型明显高于SAP组(P<0.05),C等位基因在ACS组中分布频率明显高于SAP组(P<0.01)。在冠心病组中,3种等位基因型间体重指数、总胆固醇、总甘油三脂、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、极低密度脂蛋白胆固醇等临床指标的比较无显著性差异。结论ABCA1基因启动子区-191G/CSNP在不影响中国冠心病人群血脂水平的情况下增加冠心病的发生,C等位基因与冠心病的稳定性相关。

Objective To investigate the effect of -191G/C single nucleotide polymorphisms (SNP) in the promoter region of ATP-binding cassette transporter A1(ABCA1) gene on plasma lipids and its significance in coronary artery disease (CAD). Methods By polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), -191G/C SNP in the promoter region of ABCA1 gene was analyzed in 204 patients with CAD and 114 control subjects and the distribution of the -191G/C genotypes compared between the two groups and also between different clinical phenotypes of CAD. The clinical indexes associated with CAD were also compared between the patients with the three genotypes of CAD. Results The frequency distribution of GG, GC, and CC genotypes significantly differed between CAD group and the control group, and the former group had obvious higher CC genotype frequency and the C allele frequency (P<0.05 and P<0.01, respectively). In CAD patients, the frequency distribution of GG, GC, and CC genotypes varied significantly between those with acute coronary syndrome (ACS) and those with stable angina pectoris (SAP). The CC genotype showed obviously higher frequency in ACS group than in SAP group and the C allele was more frequent in the former group (P<0.05 and P<0.01, respectively). However, no significant difference was noted in the body mass index, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, or very low-density lipoprotein cholesterols between the three genotypes. Conclusions The -191G/C SNP in the promoter region of ABCA1 is associated with increased CAD and the C allele may relate to the stability of CAD without detectable changes in plasma lipids.