ABCA1基因启动子区-14bp和ZNF位点多态性与血脂水平及冠心病易感性的关联分析

Association between --14 bp and ZNF polymorphisms of ABCAI gene promoter and high density lipoprotein cholesterol level and cardiovascular disease

目的检测三磷酸腺昔结合盒转运子A1（ATP-bindingcassettetransporterA1，ABCAl）基因启动子区-14bp及-220bp锌指蛋白可变数目串联重复序列（variable number of tandemrepeats-zinc finger protein，VNTR-ZNF）多态性与天津市汉族人群冠状动脉粥样硬化性心脏病（coronaryheartdisease，CHD）易感性及血脂水平的关联。方法采用病例对照研究，用聚合酶链反应一限制性片段长度多态性方法对260例经冠状动脉造影确诊的CHD患者和220名健康对照进行ABCA1基因-14bpC／T以及VNTR-ZNF位点ACCCC插入和缺失检测，探讨不同基因型与血脂水平及CHD易感性的关联。结果ABCA1基因-14bp位点多态性检测显示，全部检测人群中CC基因型占42．7％，CT型占51．5％，TT型占5．8％。CHD组与对照组的基因型频率及等位基因频率差异均无统计学意义（P〉O．05）；T等位基因携带者高密度脂蛋白胆固醇水平低于非携带者（P〈O．05）。ABCA1基因VNTR-ZNF位点全部检测人群中基因型分别为插入型6．2％，缺失型43．8％，插入及缺失型50．0％。两组间基因型频率及等位基因频率比较差异无统计学意义（P〉0．05）。血浆高密度脂蛋白胆固醇水平在各基因型间差异亦无统计学意义（P〉0．05）。结论ABCA1基因-14bp及VNTR-ZNF位点多态性与CHD发生无相关性。-14bp位点T等位基因携带者血浆高密度脂蛋白胆固醇水平低下。

Objective To investigate the association between polymorphisms at --14 bp and zinc finger protein（ZNF） sites of ATP-binding cassette transporter A1 （ABCA1）gene promotor and high density lipoprotein-cholesterol（HDL-C） level and coronary heart disease （CHD）. Methods Polymorphisms of Bme13901 restriction site at --14 bp and an insertion/deletion site of ACCCC in variable number of tandem repeats-zinc finger protein（VNTR-ZNF） of ABCA1 gene were detected using PCR in 260 CHD patients and 220 healthy subjects from a Chinese population in Tianjin. Results CT genotype was most common in both groups with no differences found in between（P〉0.05）. No differences were found in the frequencies of the rare T allele for --14 bp（P〉0.05）. For the --14 bp site, subjects with CT/TT genotype had a lower serum mean concentration of HDL-C compared with those with the CC genotype（P〈0.05）. Genotypic frequencies of VNTR-ZNF were 6.20% for the inserted form, 43.8% for the deleted form and 50.0% for the inserted/deleted form. No significant difference was found in the distribution of allele and genotype, or in the levels of HDL C between the two groups（P〉0.05）. Conclusion The genotypes at --14 bp of ABCA1 gene are associated with the plasma level of HDL-C. HDL-C levels in T allele carriers were significantly lower （P〈0.05）. No association was found between variations in ABCA1 VNTR-ZNF and plasma levels of HDL-C, or between the ABCA1 --14 bp and VNTR-ZNF polymorphisms and susceptibility for CHD.