宁波地区汉族人群冠心病候选基因变异及其临床的关联性

Association of candidate gene variants with clinical features of coronary artery disease in Ningbo Han population

目的:探讨CETP-Taq1B,LPL-HindⅢ及LPL-PvuⅡ基因变异对宁波地区汉族人群血脂代谢及冠心病临床表型的影响.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,男性75.1%,平均年龄(61±10)岁.其中冠心病组111例,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AB-CA1-G596A单核苷酸多态性(SNPs).结果:宁波地区汉族人群CETP-Taq1B基因型B1B1,B1B2及B2B2分布频率依次为0.39,0.49及0.11;LPL-HindⅢ基因型H+H+,H+H-及H-H-频率分别为0.58,0.39及0.03;LPL-PvuⅡ基因型P+P+,P+P-及P-P-频率分别为0.38,0.55及0.07.宁波地区CETP-Taq1B变异升高HDL水平(P=0.01),同时对TG亦有降低趋势(P=0.06);LPL-HindⅢ及PvuⅡ对HDL-C均无显著影响,而LPL-HindⅢ及PvuⅡ基因变异均显著降低血浆TG水平(P=0.001,P=0.04);3种SNP对血浆总胆固醇及LDL均无显著影响.冠心病与对照组之间上述3种变异基因型频率分布均无显著性差异(P>0.05).结论:冠心病候选基因CETP-Taq1B,LPL-HindⅢ及LPL-PvuⅡ变异对血脂代谢产生一定的影响,但与冠心病临床表型之间缺乏显著性关联.

AIM： To investigate the effects of varcation of CETP- TaqlB, LPL-HindⅢ and LPL-PvuⅡ genes on plasma lipid metabolism and clinical features of coronary artery disease in Ningbo Han population. METHODS： Totally 186 patients undertaking coronary angiography were recruited from Ningbo district, including 111 patients with coronary artery disease （CAD） and 75 controls. Male subjects accounted for 75.1% and aged （61 ± 10） years, The DNA was extracted from peripheral white blood cells by proteinase K digestion, phenol and chloroform extraction as well as isopropanol precipitation. The single nucleotide polymorphisms （ SNPs ） of cholesterol ester transfer protein （ CETP）Taq1B, Lipoprotein Lipase （LPL）-Hindm and LPL-Pvu Ⅱ were genotyped by PCR-RFLP, and verified by gene sequencing. RESULTS： Genotype frequencies of CETP-Taq1 B, LPL-Hind Ⅲ andLPL-PvuⅡ variants were 0.39,0.49 and 0. 11 for B1B1, B1B2 and B2B2, 0.58, 0.39 and 0.03 for H^＋H^＋ , H^＋H^- and H^-H^- , 0.38, 0.55 and 0.07 for P^＋P^＋ , P^＋P^- and P^-P^- , respectively. HDL-C level was siginificantly higher in CETP-B1B1 carriers than in B2B2 carriers （P=0.01）, while TG level had a trend of decrease （ P = 0.06）. SNPs of LPL-Hind Ⅲ and LPL-Pvu Ⅱ predicted plasma TG level （P=0.001 and P=0.04）. Three SNPs were not significantly associated with the plasma total cholesterol and LDL-C levels, However, CETP-Taq1B, LPL-Hind Ⅲ and LPL-Pvu Ⅱ variants were not predictive of the presence of coronary angiographic defined coronary artery disease in Ningbo district Han population （ P 〉 0.05 ）, CONCLUSION： CETP- TaqlB, LPL-HindⅢ and LPL-PvuⅡ variant exert effects on plasma HDL-C and TG levels rather than angiographic coronary artery disease.