Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Polymorphisms of Genes Related to Phase-II Metabolism and the Resistance of Clopidogrel

Version 1 : Received: 6 July 2021 / Approved: 8 July 2021 / Online: 8 July 2021 (13:30:31 CEST)

A peer-reviewed article of this Preprint also exists.

Journal reference: Future Medicine 2021
DOI: 10.2217/pgs-2021-0092


Clopidogrel is one of the thienopyridine antiplatelet drugs commonly used as a prophylactic medication to prevent coagulation in vessels and cardiovascular events. The molecule of clopidogrel is metabolized in the liver via phase-I and phase-II metabolism pathways. The sulfenic acid clopidogrel metabolite undergoes phase-II metabolism through conjugation with glutathione by the glutathione-s-transferase (GST) to form a glutathione conjugate of clopidogrel (inactive metabolite). A glutaredoxin enzyme removes the glutathione conjugated with clopidogrel to form cis-thiol-clopidogrel. This review focused on the polymorphisms of genes related to phase-II metabolism during the clopidogrel bioactivation process. Overall, no well-controlled studies were done about the relationship between the clopidogrel bioactivation process and genes related to phase-II metabolism’s enzymes. Nevertheless, some polymorphisms of G6PD, GCLC, GCLM, GSS, GST, GSR, HK, and GLRX genes could be responsible for clopidogrel resistance due to low glutathione conjugate or glutaredoxin plasma levels. Studies needed to be concerned with the relationship between clopidogrel resistance and phase-II metabolism issues in the near future.


Polymorphism; genes; phase-II metabolism; glutathione; clopidogrel resistance

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