Polymorphisms of genes related to phase II metabolism and resistance to clopidogrel

Abstract

Clopidogrel is an antiplatelet drug commonly used to prevent coagulation. This review aimed to investigate the effect of polymorphisms of G6PD, GCLC, GCLM, GSS, GST, GSR, HK and GLRX genes on clopidogrel during phase II metabolism through exploring previous studies. The results revealed that low glutathione plasma levels caused by several alleles related to these genes could affect the bioactivation process of the clopidogrel prodrug, making it unable to inhibit platelet aggregation perfectly and thus leading to severe consequences in patients with a high risk of blood coagulation. However, the study recommends platelet reactivity tests to predict clopidogrel efficacy rather than studying gene mutations, as most of these mutations are rare and other nongenetic factors could affect the drug's efficacy.

Keywords: clopidogrel resistance; genes; glutathione; phase II metabolism; polymorphism.