Pharmacogenetic Variations Related to Clopidogrel Resistance and Its Clinical Implications: An Issue Which Remains Largely Unaddressed

Abstract

Objectives: Antiplatelet therapy with either clopidogrel alone or in combination with aspirin is the mainstay prophylactic drug therapy followingpercutaneous coronary intervention and long-term prevention of cardiovascular and cerebrovascular events. Non-responders/semi-responders toclopidogrel are reported to have increased incidences of adverse outcomes like recurrent ischemic attacks. Variability in response to clopidogrel ismore common among Asians, and it is as high as 70% in some of the Asian communities. Researchers attribute inter-individual variations in responseto clopidogrel to various pharmacogenetic determinants. Polymorphisms of multidrug resistance protein 1, CYP2C19 and its alleles, P2Yadenosine diphosphate (ADP) receptor are concluded to be specific to clopidogrel resistance in Indian population.Methods: A thorough literature search was done use different keywords such as clopidogrel resistance, pharmacogenomics, pharmacogeneticvariability, and ethnic variability from database sources such as Google Scholar, Medline, PubMed Central, and Scopus.Results and Conclusion: Literature revealed a disparity between various pharmacogenetic determinants of clopidogrel resistance, particularly inthe Asian population. Few studies suggest that there is no significant association between clopidogrel response variability and ADP receptor P2Yand P2Y gene polymorphisms. Variation in the cytochrome P450 2C19 (CYP2C19) gene coding for the CYP2C19 enzyme, involved in metabolismand conversion of the clopidogrel to active metabolites is considered one of the major determinants of clopidogrel resistance in some populations.Pooled data from various studies suggest that variability in clopidogrel response cannot be attributed to a single gene polymorphism and is thoughtto be multifactorial. However, disparity in the data related to the specific gene polymorphisms responsible for the encountered clopidogrel resistancenecessitates the further evaluation of genome.12Keywords: Clopidogrel, Clopidogrel resistance, Single gene polymorphisms, Inter-individual variability.1, and P2Y121

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