P2Y12基因多态性与冠心病患者氯吡格雷抵抗的相关性研究  

Relationship between P2Y12 gene polymorphisms and clopidogrel resistance in patients with coronary heart disease

作　　者：张文斌[1] 张新霞[1] 陈晓燕[1] 莫怡浩[1] 伍贵富[1] 

机构地区：[1]广东医学院附属深圳市福田人民医院心内科,518033

出　　处：《中国心血管杂志》2015年第1期18-22,共5页Chinese Journal of Cardiovascular Medicine

基　　金：广东省医学科学技术研究基金(WSTJJ20121115)~~

摘　　要：目的探讨冠心病患者血小板二磷酸腺苷(ADP)受体亚基12(P2Y12)基因多态性位点rs6798347的分布特征及其与氯吡格雷抵抗的相关性。方法入选91例经冠状动脉造影或CT冠状动脉造影确诊的冠心病患者。给予充分的氯吡格雷治疗后,运用富血小板血浆光学法来测定患者服药后最大血小板聚集率。根据最大血小板聚集率将患者分成氯吡格雷抵抗组(CR)30例和非氯吡格雷抵抗组(NCR)61例。应用Mass ARRAY时间飞行质谱技术对患者P2Y12基因单核苷酸多态性位点rs6798347进行基因分型,比较两组患者基因型的分布情况以及不同基因型之间血小板聚集率的差异。结果 91例患者rs6798347成功分型90例,其中CR组(29例)的GG、AA、AG基因型分别有14例(48.28%)、5例(17.24%)、10例(34.48%);NCR组(61例)的GG、AA、AG基因型分别有33例(54.10%)、5例(8.20%)、23例(37.70%)。两组基因型分布差异无统计学意义(均为P>0.05),携带突变型等位基因A的患者服氯吡格雷后最大血小板聚集率有升高趋势(45.21%±16.67%比51.63%±16.18%,P=0.068);部分CR的患者服用氯吡格雷后最大血小板聚集率高于其未服药时的基线值(68.70%±13.59%比58.90%±4.93%,P=0.046);各基因型之间冠状动脉病变支数的差异无统计学意义(均为P>0.05)。CR组与NCR组之间总胆固醇[(4.11±1.12)mmol/L比(4.81±1.34)mmol/L,P=0.015]和低密度脂蛋白胆固醇[(2.18±0.81)mmol/L比(2.57±0.89)mmol/L,P=0.049]水平差异均有统计学意义;但两组患者其余临床资料差异无统计学意义(均为P>0.05)。结论 (1)血小板膜P2Y12受体基因多态性位点rs6798347与冠心病患者CR的发生无明显关系;(2)血小板膜P2Y12受体基因多态性位点rs6798347的突变型等位基因可能影响氯吡格雷抗血小板聚集的能力。Objective To investigate P2Y12 genetic polymorphisms in rs6798347 and its relationship with clopidogrel resistance in patients with coronary heart disease. Methods A total of 91 patients with coronary artery disease diagnosed by coronary angiography or coronary artery CT angiography were enrolled. Platelet aggregation rate was assessed by ADP-induced light-transmittance aggregometry after the patients received adequate clopidogrel pretreatment. Patients were divided into two groups （ clopidogrel resistance group and non-clopidogrel resistance group ） according to the ADP-induced platelet aggregation percentage. The genotype of P2Y12 （ rs6798347 ） was detected by MassARRAY Time of Flight Mass Spectrometry. Genotype and allele frequency distribution were compared between the two groups. Results According to the ADP-induced platelet aggregation rate, 29 patients were defined as clopidogrel resistance and 61 as non-clopidogrel resistance. Ninety patients were genotyped successfully. GG, AA, AG genotype frequencies were 14 （ 48. 28%） , 5 （ 17. 24%） , 10 （ 34. 48%） in clopidogrel resistance group and 33 （54. 10%）, 5（8. 20%）, 23（37. 70%） in non-clopidogrel resistance group, respectively （all p〉0. 05）. Patients carrying the mutant gene had a trend of increased platelet aggregation percentage （ 45. 21% ± 16. 67% vs. 51. 63% ± 16. 18%, p =0. 068 ） . The severity of coronary artery lesions was similar in different genotypes patients （ all p 〉0. 05 ） . Conclusions （ 1 ） The single nucleotide polymorphisms of P2Y12 in rs6798347 is not associated with clopidogrel resistance in patients with coronary heart disease. （2） The mutant gene in rs6798347 may influence the antiplatelet ability of clopidogrel.

关 键 词：基因 多态性 单核苷酸 受体 嘌呤能P2Y12 动脉粥样硬化 氯吡格雷抵抗 

分 类 号：R541.4[医药卫生—心血管疾病]