候选基因ABCAl-G596A变异与冠心病发病的关系

Relationship between ABCA1-G596A Variant and the Development of Coronary Artery Disease in Ningbo Han Population

目的探讨ABCA1-G596A基因变异与宁波地区汉族人群冠心病发病的关系。方法入选宁波地区行冠状动脉造影(CAG)检查的汉族人群186例,其中冠心病组111例,非冠心病(对照)组75例。采用苯酚-氯仿-异丙醇抽提外周血白细胞全基因组DNA,通过聚合酶链式反应(PCR)及限制性片段长度多态性(RFLP)结合测序方法确定候选基因ABCA1-G596A单核苷酸多态性(SNPs)。结果宁波地区汉族人群ABCA1-G596A基因型GG、GA及AA分布频率依次为0.34、0.37及0.29。ABCA1-G596A变异基因型GG、GA及AA携带者血浆HDL-c水平呈剂量依赖性升高(P<0.01),甘油三酯水平呈剂量依赖性降低(P<0.05),而对血浆总胆固醇及LDL-c水平无影响。冠心病组与对照组之间ABCA1-G596A变异基因型频率分布无显著性差异(P>0.05)。结论冠心病候选基因ABCA1-G596A变异对血脂代谢产生明显的影响,但与冠心病发病无显著性关联。

Objective To explore the relationship between ABCA1-G596A genetic variant and clinical phenotype associated with the development of coronary artery disease in Chinese Han population in Ningbo. Methods Total of 186 cases undertaken coronary angiography were recnalted from Ningbo district, including 111 patients with coronary artery disease （CAD） and 75 people without coronary artery disease （controls）. Their age was 61 ± 10 years and the male accounted for 75.1%. The DNA was extracted from peripheral white blood cell by approach comprised proteinase K digestion, phenol and chloroform extraction as well as isopropanol precipitation. The SNP of ATP-binding cassette transporter （ABCA1）-G596A was genotyped by PCR-RFLP, and verified by gene sequencing. Results Genotyptic frequencies of ABCA1-G596A variant were 0.34,0.37 and 0.29 across GG, GA and AA genotype, respectively. SNP of ABCA1-G596A predicted plasma HDL-c level （GG 45.3 ± 11.4mg/dL, GA 46.5 ± 12.0 mg/dL and AA 49.2 ± 13.6mg/ dL, P = 0.001）. Meanwhile, ABCA1-G596A variant was associated with significant changes of of levels （GG 189.0± 106.8 mg/ dL, GA 173.1 ± 88.2 mg/dL and AA 155.6 ± 102.4 mg/dL, P = 0.01）, while ABCA1-G596A variant was not associated with the plasma total cholesterol and LDL-c levels. However, ABCA1-G596A was not predictive of the presence of coronary angiographic defreed coronary artery disease in Chinese Han population （ P 〉 0.05）. Conclusions ABCA1-G596A variant predicted differences in risk-related plasma HDL-c and TG levels rather than angiographic coronary artery disease. The discrepancy indicates the complexity in etiology of coronary artery disease.