ABCA1基因编码区SNP检测及R1587K与血脂和冠心病的关系

Detection of single nucleotide polymorphism of all coding region in ABCA1 gene and relationship among R1587K and plasma lipids and coronary artery disease

目的探讨三磷酸腺苷结合盒转运子A1基因ABCA1 R1587K单核苷酸多态性（SNP）在中国广东汉族人群中的发生情况及该多态性与脂代谢和冠心病易感性的关系。方法选择确诊的冠心病患者112例和同地区正常人108例，以引物引入限制性内切酶分析聚合酶链反应（PIRA-PCR）方法对ABCA1的R1587K多态性进行检测，并进行血脂水平检测。结果全部检测人群中RR型占49．1％，RK型占44．1％，KK型占6．8％。等位基因频率符合Hardy-Weinberg平衡，冠心病及正常人中R携带者HDLc水平均明显高于非携带者（P〈0．01）。在ABCA1的RR、RK和KK3种基因型中，HDI，C水平依次下降（分别1．35±0．29、1．24±0．27、0．77±0．21mmol／L，P〈0.01）。多重回归分析提示，R1587K基因型与HDL-C水平有显著相关（P=0．000）。冠心病患者与正常人等位基因频率、基因型频率差异无显著性（P〉0.05）。K基因型携带者与非携带者患冠心病的风险无显著性差异（OR=0．889，95％CI=0．49～1．61，P〉0.05）。结论ABCA1基因编码区R1587K携带情况与人群血浆HDL-C水平密切相关，K携带者血浆HDL-C水平明显下降，但与冠心病患病风险无明显相关性。

Objective To investigate the distribution of R1587K polymorphism of ATP-binding cassette transporter A1 （ABCA1） gene in Han Nationality population in Guangdong and its relation to plasma lipid level and susceptibility to coronary artery disease （CAD）. Methods Genotypes of ABCA1 R1587K polymorphlsm were determined by primer-introduced restriction analysis＇-PCR technique in 112 CAD cases and 108 healthy people. Results 49. 1% of the examined subjects belonged to the genotype of RR, 44. 1% belonged to RK, and 6. 8% belonged to KK. The observed allele frequencies fit well with the Hardy-Weinberg equilibrium. The levels of high-density lipoprotein cholesterol （HDL-C） of 1587R allele carriers were obviously higher than those of 1587R non-carriers in CHD group and controls respectively （P〈0. 01 and P〈0. 01）. The levels of HDL-C showed a declined trend （P〈0. 01） in the sequence of RR, RK and KK genotypes with a significant difference among RR genotype （1.35-t-0. 29rrmaol/L）, RK genotype （1. 24±0. 27 mmol/L） and KK genotype （0.77±0. 21mmol/L）. Moreover, the multiple regression analysis showed that the R1587K genotype significantly correlated with the levels of HDL-C （P〈0. 01）. Neither the frequencies of R1587K alleles nor genotypes showed significant differences between CAD patients and control （P〉0. 05）, and there were no significant differences of the risk for coronary artery disease between K allele carriers and K noncarriers （OR=0. 889; 95%CI=0. 49-1. 61; P〉0. 05）. Conclusion The genotypes of ABCA1 R1587K polymorphism were associated closely with the plasma levels of HDL-C. The HDL-C levels of K allele carriers were remarkably lower. However, there was no significant association of the ABCA1 R1587K polymorphism and the susceptibility to CAD.