急性冠状动脉综合征患者氯吡格雷代谢基因多态性分析  

Clopidogrel metabolism related gene polymorphisms in Chinese patients with acute coronary syndrome

作　　者：冯广迅[1] 梁岩[1] 白莹[1] 陈涛[1] 刘欣[3] 杨艳敏[1] 王兴宇[3] 杨跃进[2] 朱俊[1] 

机构地区：[1]中国医学科学院北京协和医学院阜外心血管病医院急重症中心,100037 [2]中国医学科学院北京协和医学院阜外心血管病医院冠心病诊治中心,100037 [3]北京高血压联盟研究所

出　　处：《中华心血管病杂志》2012年第11期908-913,共6页Chinese Journal of Cardiology

摘　　要：目的通过对急性冠状动脉综合征（ACS）患者CYP2C19，ABCB1和对氧磷酸酶（PON）1基因多态性的检测，了解我国ACS患者氯吡格雷代谢基因多态性的分布特点。方法选取2005至2008年期间人住北京阜外医院、临床诊断为ACS且症状发生4周内的患者作为研究对象。通过TaqMan实时定量PCR方法检测与氯吡格雷代谢相关的CYP2C19＊2-＊8，＊17，ABCB1 C3435T，PON1 Q192R及L55M基因多态性，计算次要等位基因频率（MAF），并将患者按CYP2C19携带情况分为不同代谢类型：强代谢型：未携带任何功能缺失（LOF）等位基因或功能增强（GOF）等位基因，即＊1／＊1；中间代谢型：携带有1个LOF等位基因，即＊1／＊2-＊8；弱代谢型：携带有2个LOF等位基因，即＊2-＊8／＊2-＊8；超代谢型：携带有1个或2个GOF等位基因，即＊1／＊17或＊17／＊17；不明代谢型：同时携带1个LOF等位基因和1个GOF等位基因，即＊2-＊8／＊17。结果2800例ACS患者中，平均年龄为（59．0±12．3）岁，男性2236例（79．9％），ST段抬高型心肌梗死2072例（74．0％），非ST段抬高型心肌梗死617例（22．0％），不稳定性心绞痛111例（4．0％）。2800例患者中，CYP2C19 ＊2，＊3，＊4，＊17的MAF分别为28．7％，4．6％，0．1％和1．2％，未发现CYP2C19基因LOF位点＊5-＊8。代谢分型：强代谢型41．7％，中间代谢型45．6％，弱代谢型10．3％，超代谢型1．9％和不明代谢型0．6％。ABCB1 C3435T，PON1 Q192R和PON1 L55M多态位点MAF分别为39．4％，37．8％和4．4％。不同性别在所有基因分型上差异无统计学意义。ACS患者总CYP2C19的LOF等位基因携带率为56．4％，GOF携带率为2．5％。结论提示在我国ACS人群中有较高的CYP2C19氯毗格雷代谢LOF等位基因分布。Objective To detect the single nucleotide polymorphisms of clopidogrel metabolism related genes （CYP2C19, ABCB1 and PON1 ） in Chinese patients with acute coronary syndrome（ACS） by genotype analysis. Methods Genetic analysis was performed in patients admitted to Fuwai Hospital from 2005 to 2008 with ACS within 4 weeks. The detection of polymorphisms was performed by TaqMan real-time PCR method. The alleles genotyped were CYP2C19 ＊ 2- ＊ 8, ＊ 17, ABCB1 C3435T, PON1 Q192R and PON1 L55M. Minor allele frequency （MAF） was calculated. Patients were classified as one of the 5 categories by clopidogrel metabolizer phenotypes as extensive [without any ＂loss-of-function＂ （LOF） allele ＊ 2- ＊ 8 or ＂gain-of-function＂ （GOF） allele ＊ 17 ] , intermediate （ with only one LOF allele）, Poor （ with two or more LOF alleles）, ultra （with one or two GOF alleles） or unknown （with one LOF allele and one GOF allele）. Results A total of 2800 ACS patients were enrolled [ mean age （59. 0 ±12. 3 ） years and 2236 males（79. 9% ） ]. There were 74% patients with ST-segment elevation myocardial infarction （ STEMI, n =2072）, 22.0% patients with non-ST-segment elevation myocardial infarction （NSTEMI, n = 617 ）and 4. 0% patients with unstable angina （UA, n = 111 ）. The minor allele frequency （MAF） for each genotype of CYP2C19 ＊2, ＊3, ＊4, ＊17 was 28. 7% , 4. 6% , 0. 1% andl. 2% , respectively. There was noLOF allele ＊ 5 - ＊ 8 in the study population. The MAF for ABCB1 C3435T, PON1 Q192R and PON1 L55M was 39.4%, 37. 8% and 4.4%, respectively. Clopidogrel metabolizer groups were defined as extensive in 41.7%, intermediate in 45.6%, poor in 10. 3%, ultra in 1.9% and unknown in 0. 6% patients, respectively. There were no significant differences for all genotypes between males and females. Total LOF carriers of CYP2C19 were 56. 4% and GOF carriers were 2. 5%. Conclusions Our study demonstrated a high distribution of the LOF allele of CYP2C19 in China ACS population.

关 键 词：冠状动脉疾病 血小板聚集抑制剂 多态性 单核苷酸 

分 类 号：R541.4[医药卫生—心血管疾病]