Key result
Polymorphisms in phase II metabolism genes may impair clopidogrel bioactivation by lowering glutathione levels, though platelet reactivity tests are recommended over genetic testing.
Why the study?
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.
Do polymorphisms in phase II metabolism genes affect clopidogrel efficacy in patients at high risk of blood coagulation?
Do polymorphisms in phase II metabolism genes affect clopidogrel efficacy in patients at high risk of blood coagulation?
While phase II metabolism gene polymorphisms can impair clopidogrel bioactivation, platelet reactivity testing is more practical than genetic testing for predicting efficacy.
Gene variants affecting glutathione may blunt clopidogrel response; hypothesis-generating for pharmacogenomic testing pending larger trials.
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.
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Alkattan et al. (2021) conducted a review in High risk of blood coagulation. Polymorphisms of G6PD, GCLC, GCLM, GSS, GST, GSR, HK and GLRX genes was evaluated on Clopidogrel bioactivation and platelet aggregation inhibition. Polymorphisms in phase II metabolism genes may impair clopidogrel bioactivation by lowering glutathione levels, though platelet reactivity tests are recommended over genetic testing.
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