期刊文献+

Effects of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and clinical outcome in patients with acute coronary syndromes undergoing stent-based coronary intervention 被引量:15

Effects of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and clinical outcome in patients with acute coronary syndromes undergoing stent-based coronary intervention
原文传递
导出
摘要 Background The CYP2C19 G681A single polymorphism has been proven to affect clopidogrel responsiveness. However, the effect of coexisting polymorphisms of other genes has not yet been reported in the Chinese population. This study investigated the effect of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and adverse clinical events in Chinese patients. Methods In 577 Han Chinese patients undergoing stent placement because of acute coronary syndrome had platelet reactivity assessed by thromboelastography, and the CYP2C19 G681A and P2Y12 C34T polymorphisms were detected by the ligase detection reaction. Primary clinical endpoints included cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis. The secondary clinical endpoints were thrombolysis in myocardial infarction bleeding. The follow-up period was 12 months. Results Genotyping revealed 194 carriers of the wild type GG genotype of CYP2C19 and the wild type CC genotype of P2Y12 (group 1), 102 carriers of the wild type GG genotype of CYP2C19 and the mutational T allele of P2Y12 (group 2), 163 carriers of the mutational A allele of CYP2C19 and the wild type CC genotype of P2Y12 (group 3), and 118 carriers of the mutational A allele of CYP2C19 and the mutational T allele of P2Y12 (group 4). Group 4 had the lowest ADP-inhibition (49.74+32.61) and the highest prevalence of clopidogrel low response (29.7%) of the four groups. The rate of the composite of primary clinical endpoints increased more in group 4 (8.5%) than in the other three groups; the rate of composite primary endpoints in group 2 (2.9%) and group 3 (3.7%) were not significantly different than that of group 1 (1.5%). Conclusion Coexisting polymorphisms of different genes affected clopidogrel responsiveness and clinical outcome more than single polymorphism in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention. Background The CYP2C19 G681A single polymorphism has been proven to affect clopidogrel responsiveness. However, the effect of coexisting polymorphisms of other genes has not yet been reported in the Chinese population. This study investigated the effect of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and adverse clinical events in Chinese patients. Methods In 577 Han Chinese patients undergoing stent placement because of acute coronary syndrome had platelet reactivity assessed by thromboelastography, and the CYP2C19 G681A and P2Y12 C34T polymorphisms were detected by the ligase detection reaction. Primary clinical endpoints included cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis. The secondary clinical endpoints were thrombolysis in myocardial infarction bleeding. The follow-up period was 12 months. Results Genotyping revealed 194 carriers of the wild type GG genotype of CYP2C19 and the wild type CC genotype of P2Y12 (group 1), 102 carriers of the wild type GG genotype of CYP2C19 and the mutational T allele of P2Y12 (group 2), 163 carriers of the mutational A allele of CYP2C19 and the wild type CC genotype of P2Y12 (group 3), and 118 carriers of the mutational A allele of CYP2C19 and the mutational T allele of P2Y12 (group 4). Group 4 had the lowest ADP-inhibition (49.74+32.61) and the highest prevalence of clopidogrel low response (29.7%) of the four groups. The rate of the composite of primary clinical endpoints increased more in group 4 (8.5%) than in the other three groups; the rate of composite primary endpoints in group 2 (2.9%) and group 3 (3.7%) were not significantly different than that of group 1 (1.5%). Conclusion Coexisting polymorphisms of different genes affected clopidogrel responsiveness and clinical outcome more than single polymorphism in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention.
出处 《Chinese Medical Journal》 SCIE CAS CSCD 2013年第6期1069-1075,共7页 中华医学杂志(英文版)
关键词 CLOPIDOGREL acute coronary syndromes CYP2 C19 P2 Y12 platelet reactivity clopidogrel acute coronary syndromes CYP2 C19 P2 Y12 platelet reactivity
  • 相关文献

参考文献3

二级参考文献32

  • 1Gurbel PA,Bliden KP,Hayes KM,Yoho JA,Herzog WR,Tantry US.The relation of dosing to clopidogrel responsiveness and the incidence of high post-treatment platelet aggregation in patients undergoing coronary stenting.J Am Coll Cardiol 2005; 45:1392-1396.
  • 2Desai NR,Mega JL,Jiang S,Cannon CP,Sabatine MS.Interaction between cigarette smoking and clinical benefit of clopidogrel.J Am Coll Cardio12009; 53:1273-1278.
  • 3de Morais SM,Wilkinson GR,Blaisdell J,Nakamura K,Meyer UA,Goldstein JA.The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans.J Biol Chem 1994; 269:15419-15422.
  • 4Goldstein JA.Clinical relevance of genetic polymorphisms in the human CYP2C subfamily.Br J Clin Pharmacol 2001; 52:349-355.
  • 5Bertilsson L.Geographical/interracial differences in polymorphic drug oxidation.Current state of knowledge of cytochromes P450 (CYP) 2D6 and 2C19.Clin Pharmacokinet 1995; 29:192-209.
  • 6Motovska Z,Widimsky P,Petr R,Bilkova D,Marinov I,Simek S,et al.Factors influencing clopidogrel efficacy in patients with stable coronary artery disease undergoing elective percutaneous coronary intervention:statin's advantage and the smoking "paradox".J Cardiovasc Pharmacol 2009; 53:368-372.
  • 7Price MJ,Nayak KR,Barker CM,Kandzari DE,Teirstein PS.Predictors of heightened platelet reactivity despite dual-antiplatelet therapy in patients undergoing percutaneous coronary intervention.Am J Cardiol 2009; 103:1339-1343.
  • 8Yang G,Fan L,Tan J,Qi G,Zhang Y,Samet JM,et al.Smoking in China:findings of the 1996 National Prevalence Survey.JAMA 1999; 282:1247-1253.
  • 9Gu D,Wu X,Reynolds K,Duan X,Xin X,Reynolds RF,et al.Cigarette smoking and exposure to environmental tobacco smoke in China:the international collaborative study of cardiovascular disease in Asia.Am J Public Health 2004; 94:1972-1976.
  • 10Varenhorst C,James S,Erlinge D,Brandt JT,Braun OO,Man M,et al.Genetic variation of CYP2C19 affects both pharmacokinetic and pharmacodynamic responses to clopidogrel but not prasugrel in aspirin-treated patients with coronary artery disease.Eur Heart J 2009; 30:1744-1752.

共引文献62

同被引文献62

引证文献15

二级引证文献85

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部