中国汉族人群冠心病候选基因变异及其临床关联的地域特征  

Geographical characteristics of single nucleotide polymorphism of candidate genes associated with coronary artery disease in Chinese Hart population

作　　者：王胜煌[1] 崔翰斌[2] 王东琦[3] 陈晓敏[1] 张宏考[4] 崔长琮[3] 陈新义[2] 刘新宏[2] 张征[5] 白锋[5] Muhlestein JB 

机构地区：[1]浙江省宁波市第一医院心脏内科,315010 [2]陕西省人民医院心脏内科 [3]西安交通大学第一附属医院心脏内剩 [4]湖北省十堰市人民医院心脏内科 [5]兰州大学第一附属医院心脏内科 [6]美国犹他大学LDS医院

出　　处：《中华心血管病杂志》2008年第1期24-29,共6页Chinese Journal of Cardiology

基　　金：2003美国沙漠基金资助项目

摘　　要：目的探讨冠心病候选基因单核苷酸多态性在中国汉族人群中的地域分布特征。方法选择西安、十堰及宁波地区汉族人群中经冠状动脉造影证实的冠心病及正常对照为研究对象。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单核苷酸多态性（SNP）。SNP位点选择ATP结合盒转运子（ABCA1-G596A），胆固醇酯转运蛋白（CETP-Taq1B），脂蛋白脂酶（LPL-HindⅢ及LPL-PvuⅡ）。结果入选西安、十堰及宁波三个地区中国汉族人群615例（西安、十堰及宁波地区分别220、209及186例），平均年龄（60±10）岁，男性占75．9％。西安地区人群糖尿病罹患率以及血清总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）及甘油三酯（TG）水平显著高于十堰及宁波地区人群（均P〈0．05），高密度脂蛋白胆固醇（HDL-C）水平显著低于后者[分别为（1．17±0．48）mmol／L，（1．25±0．33）mmol／L，（1．29±0．44）mmol／L，P=0．03]；三个地区人群之间ABCA1-G596A及CETP-Taq1B基因型频率分布差异具有统计学意义（均P〈0．01），而LPL基因型频率基本一致（P〉0．05）；4个SNP对三个地区人群TC及LDL-C影响差异无统计学意义。ABCA1-G596A基因变异均显著升高三个地区人群血浆HDL-C水平（P〈0．01），同时降低TG水平[西安：GG（2．4±1．3）mmol／L、GA（1．9±0．9）mmol／L、AA（1．6±0．8）mmol／L，P〈0．01；十堰：GG（2．1±1．0）mmol／L、GA（1．9±0．8）mmol／L、AA（1．8±0．7）mmol／L，P=0．03；宁波：GG（1．9±1．1）mmol／L、GA（1．8±0．9）mmol／L、AA（1．6±0．7）mmol／L，P=0．05]；三个地区人群LPL-HindⅢ（＋／＋）基因型携带者血浆TG均水平显著高于（-／-）携带者[西安：＋／＋（2．2±1．0）mmol／L、-／-（1．6±0．7）mmol／L，Objective To investigate the geographical characteristics of single nucleotide polymorphism （SNP） of candidate genes associated with coronary artery disease in Chinese Han population. Methods Study population were Chinese Han nationality recruited from Xi＇ an, Shiyan and Ningbo districts. Patients with coronary artery disease were defined by coronary angiography with stenosis ≥ 50% and control subjects with stenosis 〈 10%, respectively. 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, cholesteryl ester transfer protein （CETP）-Taq1B, Lipoprotein lipase （LPL）-Hind Ⅲ and LPL-Pvu Ⅱ were genotyped by PCR-RFLPs, and verified by gene sequencing. Results A Total of 615 patients undertaken coronary angiography were recruited from cardiac center in Xi＇an （220）, Ningbo （209） and Shiyan district （ 186）, China （mean age 60 ± 10 years, 75.9% males）. Diabetes melitus was more prevalent in Xi＇an Cohort population than Shiyan and Ningbo cohort （ P 〈 0. 01 ）. Plasma total cholesterol, LDL cholesteol and triglyceride levels in Xi＇an Cohort population were significantly higher, and HDL-C siginificantly lower than in Shiyan and Ningbo cohort population [ HDL-C ： （ 1.17 ± 0.48） mmol/L vs. （ 1.25 ± 0. 33 ） mmol/L and （ 1.29 ± 0.44 ） mmol/L, P 〈 0. 05 ] . Distribution differences for ABCA1-G596A and CETP-Taq1B genotypes were found in Xi＇ an Cohort population compared to Ningbo and Shiyan cohorts （for ABCA1, Xi＇an： 0. 24, 0. 53, 0. 23 and Shiyan： 0. 17, 0. 62, 0. 21 and Ningbo： 0. 34, 0. 37, 0. 29,for GG, AG, AA, respectively, P〈0.01 ; and for CETP, Xi＇an： 0. 29, 0. 54, 0. 17 and Shiyan： 0. 38, 0.40, 0. 22 and Ningbo： 0. 39, 0.49, 0. 12 for B1B1, B1B2, B2B2, respectively, P 〈 0. 01）, but not for LPL variants. ABCA1-G596A variant predicted HDL-C [Xi＇an： �

关 键 词：冠状动脉疾病 ATP结合匣式转运子 脂蛋白脂酶 多态性 单核苷酸 地域因素 

分 类 号：R686[医药卫生—骨科学]