汉族人群ABCA1基因R219K单核苷酸多态性分析

Study on Single-nucleotide Polymorphisms of ABCA1 R219K in Han Population

目的探讨ABCA1基因R219K多态性在汉族人群中的分布,分析其与血脂及冠心病的关系。方法采用聚合酶链反应-限制性片段长度多态性(polymerase chain reaction restriction fragment length polymorphism,PCR-RFLP)的分析方法,检测中国汉族人群中无血缘关系的132名冠心病患者和157名对照者ABCA1基因R219K位点的多态性,并通过直接测序验证。全自动生化分析仪检测血清总胆固醇(TC)、高密度脂蛋白-胆固醇(HDL-C)、低密度脂蛋白-胆固醇(LDL-C)、载脂蛋白AI(apoAI)、载脂蛋白B(apoB)及血糖的水平。分析不同基因型频率的分布特点以及与血脂、CHD的相关性。结果ABCA1基因R219K多态性基因型分布均符合Hardy-Weinberg平衡;湖南地区汉族人群中ABCA1基因R219K多态性位点存在RR、RK、KK三种基因型,发生频率分别为RR(35.3%)、RK(43.6%)、KK(21.1%);冠心病组KK基因型频率(17.4%)低于对照组(24.2%),KK基因型的HDL-C水平明显高于RR型(P<0.05);R219K各基因型中KK基因型的冠脉病变程度低于RR、RK基因型(P<0.05)。结论汉族人群中存在ABCA1基因R219K多态性;ABCA1基因R219K变异KK型产生有益的临床血脂谱,可能是冠心病患者的低危遗传标记;R219K各基因型中KK基因型的冠脉病变程度低于RR、RK基因型。

Objective To study the distribution of the R219K polymorphism in the exon 7 of ATP binding cassette transporter （ABCA1） gene in Hen population, and to analyze the association between blood lipids and coronary heart disease （CHD）. Methods Polymerase chain reaction - restriction fragment length polymorphism （PCR - RFLP） method was used to determine R219K locus mutation polymorphisms in ABCA1 gene in 132 CHD patients and 157 controls. The gene polymor- phisms were confirmed by sequencing. Automated biochemical analyzer was used to measure the serum total cholesterol （TO）, triglyceride （TG）, high density lipoprotein cholesterol （HDL - C）, low density lipoprotein cholesterol （LDL - C）, apolipoprotion AI （apoAI）, apolipoprotein B （apoB） and blood sugar. The frequencies of diverse genotypes and their association with plasma lipid levels and CHD were studied. Results The prevalence of the ABCA1 alleles and genotypes in each group were consistent with Hardy- Weinberg equilibrium law. ABCA1 gene R219K polymorphisms were existing in Han population. The frequency of ABCA1 RK genotype （43. 6%） was the highest among ABCA1 genotypes, followed by RR genotype （3.5.3 % ）, KK genotype （21.196 ）. In coronary heart disease group the KK genotype frequency （17.4 % ） was lower than that in the ,controls （24.2 % ） and the KK genotype had a higher HDL - C level （P〈 0.05）. The severity of CHD in KK genotype was lighter than that in RK and RR genotypes （P〈 0.0.5）. Conclusions The results show that there is R219K polymorphism of the ABCA1 gene in Han population. The KK genotype of ABCA1 R219K genetic variation results in a beneficial profile of blood lipids, which may be a novel genetic marker for low risk of coronary heart disease. The severity of CHD in KK genotype is lighter than those in RK and RR genotypes.