Abstract
Background: Studies have demonstrated that the mutant *2 and*3 allele of the CYP2C19 loss-of-function polymorphism is associated with diminished metabolization of clopidogrel and an attenuated platelet response to clopidogrel treatment. Since no such study has been conducted in this region, we examined CYP2C19 polymorphism in Acute Coronary Syndrome (ACS) patients on clopidogrel treatment, and its effect on the cardiovascular outcomes. Material and Methods: A total of 100 samples of ACS were included in this study and genotyping of CYP2C19 *2 and *3 gene polymorphisms was performed by a Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP). Results: The distribution of CYP2C19*2 allele wild *1/*1, Heterozygous *1/*2 and homozygous mutant *2/*2 genotypes was 56%, 34% and 10% respectively while for CYP2C19*3 wild*1/*1 and heterozygous *1/*3 genotypes was 84% and 16% respectively. The frequency of compound heterozygotes (*2/*3) was found in 9% (9 of 100 patients). CYP2C19 *1/*2 allele was found in 03 of 34 (8.8%) patients who had CV events followed by 2 of 10 (20%) patients with mutant genotype CYP2C19*2 (*2/*2) on follow up. In the CYP2C19*3, 31.2% having heterozygous genotype (*1/*3) had CV events as compared to 11.9% with *1/*1 (31% v/s 11.9% p> 0 .05). In the poor-metabolizer group (*2/*2 or *2/*3), 20.1% of patients had CV events on follow up compared to 15.6% in the extensive metabolizer group (*1/*1), whereas in the intermediate group only 10% of patients had CV events (p>0.05). Conclusion: We conclude that patients carrying CYP2C19 loss-of-function alleles had a higher rate of subsequent cardiovascular events than as against those with normal allele. Lack of significant events even in presence of variant alleles justifies us to some extent to continue clopidogrel in our patients
Highlights
The hepatic CYP2C19 enzyme contributes to the metabolism of many clinically relevant drugs such as antidepressants, benzodiazepines, mephenytoin, some proton pump inhibitors, and clopidogrel
The majority of the CYP2C19 PMs are carriers of the variant alleles *2 and *3, which are loss of function alleles (LOF) whereas the *17 variant is a gain of function (GOF) allele associated with increased activity [2]
Clopidogrel is an antiplatelet drug used in atherothrombotic diseases, such as myocardial infarction and stroke, which is an inactive prodrug that needs to be bioactivated by a liver enzyme, CYP2C19
Summary
The hepatic CYP2C19 enzyme contributes to the metabolism of many clinically relevant drugs such as antidepressants, benzodiazepines, mephenytoin, some proton pump inhibitors, and clopidogrel. On the basis of their ability to metabolise (S)-mephenytoin or other probe drugs, individuals can be categorized as Extensive Metabolizer (EM), PM (Poor Metabolizer or Ultra rapid Metabolizer (UM) for CYP2C19. The allelic frequency of CYP2C19*2 has been shown to be 15% in Africans, 29–35 % in Asians, 12–15% in Caucasians and 61% in Oceanians. The CYP2C19*3 is mainly found in Asians (5–9% in Asians, less than 0.5% in Caucasians). The allelic frequency of CYP2C19*17 has been shown to be 16% in Africans, 3–6% in Asians and 16–21% in Caucasians [3]
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