The role of CYP2C19 gene polymorphisms on antiplatelet activity of clopidogrel among Arabs: systematic review and meta-analysis

Abstract

AbstractThis study aimed to predict the preventive effect of clopidogrel against recurrent cardiovascular events (CVEs) among the Arab population carrying different CYP2C19 mutations and to determine the frequency of polymorphic alleles and genotypes of CYP2C19 among them. The review included all the studies that reported data related to the CYP2C19 polymorphisms among Arab populations. The review included Arab CVDs patients who are categorized into carriers (cases) and non-carriers (controls) of CYP2C19 alleles and used clopidogrel as secondary prophylaxis. The patients who had recurrent CVEs or had high on-treatment platelet reactivity (HTPR) while using clopidogrel treatment were described as (events). The results showed a significantly increased risk of recurrent CVDs events by about three folds was associated with carriers of CYP2C19*2 and CYP2C19*3 mutations compared to non-carriers (OR= 3.32, CI=1.94-5.67, and OR=3.53, CI=1.17-10.63 respectively). However, no significant difference was recorded between both studied groups regarding the presence of CYP2C19*17 mutation (OR=0.80, (CI=0.44-1.44). The results also revealed that 59 (4.16%) of Arabs carrying two CYP2C19*2 alleles (homozygous), and 356 (25.12%) have one CYP2C19*2 allele and one CYP2C19*1 allele (heterozygous). Moreover, 42 (2.96%) were carrying two CYP2C19*17 alleles (homozygous), and 262 (18.49%) were carrying one CYP2C19*17 allele and one wild-type allele of CYP2C19 (heterozygous). The most common CYP2C19 genotypes reported among Arabs was the wild-type *1/*1, of which 49.26% of them had the homozygous form of the CYP2C19*1 allele. The frequency of the CYP2C19*1 allele was 71.07%, followed by the CYP2C19*2 allele (16.73%) and CYP2C19*17 (12.21%), respectively. The CYP2C19*3 allele was detected rarely among Arabs (<1%) compared to CYP2C19*1, *2, and *17 alleles. The present study revealed that Arabs carrying CYP2C19*2 and CYP2C19*3 alleles may not respond to clopidogrel and may put those patients at risk of recurrent CVEs. Carriers of the CYP2C19*17 allele, on the other hand, did not show a significant role either in increasing or decreasing the antiplatelet efficacy of clopidogrel. The CYP2C19 genotypes including *1/*1, *1/*2, *1/*17, *2/*2, and *17/*17 are commonly distributed among the Arabs.