CETP基因-629C／A多态性对阿托伐他汀钙调脂效应及长期临床预后的影响  

Influence of CETP gene-629C/A polymorphism on the efficacy of atorvastatin treatment and clinical outcome

作　　者：高静[1] 从洪良[2] 毛用敏[1] 刘祎[2] 张楠[2] 陈倩[1] 刘婷[1] 崔让庄[1] 

机构地区：[1]天津市胸科医院心血管病研究所,300051 [2]天津市胸科医院心内科,300051

出　　处：《中华医学遗传学杂志》2013年第5期553-558,共6页Chinese Journal of Medical Genetics

基　　金：天津市卫生局科学基金（201IKZ62）

摘　　要：目的分析中国天津地区汉族冠状动脉性心脏病（coronary heart disease，CHD）患者胆固醇酯转运蛋白（cholesteryl ester transfer protein，CETP）基因-629C／A多态性，从药物基因组学角度探讨遗传因素对于阿托伐他汀钙调脂疗效以及患者长期预后的影响，为个体化治疗提供理论依据。方法研究对象为经冠状动脉造影检查证实的CHD患者232例。应用聚合酶链反应-限制性片段长度多态性方法检测其CETP-629C／A基因型，用酶联免疫吸附测定法（enzyme—linked immunosorbent assay，ELISA）测定血清CETP含量。所有患者接受阿托伐他汀钙20mg／d调脂治疗1年后复查血脂，随访12～23个月，记录MACE事件（包括死亡、非致死性心肌梗死、再次血运重建和卒中）。采用Kaplan—Meier生存曲线Log—rank检验分析不同基因型对于生存率的影响。结果A突变等位基因频率为0．475，C等位基因频率为0．525；CC、CA、AA基因型相比，血清高密度脂蛋白胆固醇（high—density lipoprotein cholesterol，HDL—C）水平呈升高趋势，血清CETP水平呈降低趋势，但差异均无统计学意义（F=0．893，P=0．411；F=1．279，P=0．282）。血清HDL-C水平与CETP浓度呈负向变化趋势，但其相关性无统计学意义（r=0．151，P=0．081）。阿托伐他汀钙20mg／d调脂治疗1年后，CC基因型携带者低密度脂蛋白胆固醇（low—density lipoprotein cholesterol，LDL-c）水平下降最多，达35．41％，CA基因型次之，为18．84％，AA基因型下降最少，为8．15％，差异有统计学意义（P=0．001）。血清脂蛋白（a）水平变化在不同基因型3组间差异有统计学意义（P=0．021），CC基因型下降最明显，为30．41％；3种基因型患者HDL-C水平的变化尽管呈梯度变化的趋势，但差异无统计学意义（P=0．470）；CC基因型HDL-C水平升高最明显，为14．37％，CA基因型为10．48％，AA基因型为6．64％；对�Objective To investigate cholesteryl ester transfer protein （CETP） gene polymorphism -629C/A among Han Chinese patients with coronary heart disease （CHD） in Tianjin region, and to assess the influence of genetic factors on therapeutic effect of atorvastatin and clinical outcome in order to provide a pharmacogenomic basis for individual treatment. Methods From October 2010 to July 2011, 232 patients with angiographically confirmed CHD were recruited. Polymorphism of position --629 of the CETP gene promoter was determined with polymerase chain reaction-restricted fragment length potymorphism （PCR-RFLP） method. Serum level of CETP was determined with enzyme-linked immunosorbent assay （ELISA）. I.ipid level in all patients was determined at baseline and after 12 months of treatment with 20 mg/d atorvastatin. Clinical follow-up was carried out for more than a year （12-23 months）. Major adverse cardiac events including death, non-fatal infarction, revascularization and stroke （MACE） were recorded. A Kaplan-Meier log-rank test was used to compare MACE-free survival for individuals with various genotypes. Results The frequency of --629A allele was 0. 408. Compared with CC or CA genotypes, individuals with AA genotype had lower CETP levels and higher high-density lipoprotein cholesterol （HDL-C） levels, albeit without statistical significance （F=0. 893, P=0. 411 and F= 1. 279, P= 0. 282, respectively）. There also appeared to be a negative correlation between serum HDL-C and CETP levels, though no statistic significance was detected （r=--0. 151, P=0. 081）. After 12 months atorvastatin therapy, individuals with CC genotype had greater reduction of low-density lipoprotein cholesterol（LDL-C）, reduced LP（a） and elevated HDL-C compared with CA or AA genotypes. LDL-C level has decreased by 35. 41% in CC homozygotes, 18. 84% in CA heterozygotes and 8.15% in AA homozygotes （P=0. 001）. HDL-C level has increased by 14.37% in CC homozygotes, 10.48% in CA heterozygotes and 6.64% in AA homo

关 键 词：冠状动脉性心脏病 胆固醇酯转运蛋白 阿托伐他汀钙 基因多态性 药物基因组学 CETP基因 

分 类 号：R541.4[医药卫生—心血管疾病]