General and Applied Toxicology

Abstract

<h3>Abstract</h3> This study aimed to predict the preventive effect of clopidogrel against recurrent cardiovascular events (CVEs) among the Arab population carrying different <i>CYP2C19</i> mutations and to determine the frequency of polymorphic alleles and genotypes of <i>CYP2C19</i> among them. The review included all the studies that reported data related to the <i>CYP2C19</i> polymorphisms among Arab populations. The review included Arab CVDs patients who are categorized into carriers (cases) and non-carriers (controls) of <i>CYP2C19</i> 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 <i>CYP2C19*2</i> and <i>CYP2C19*3</i> 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 <i>CYP2C19*17</i> mutation (OR=0.80, (CI=0.44-1.44). The results also revealed that 59 (4.16%) of Arabs carrying two <i>CYP2C19*2</i> alleles (homozygous), and 356 (25.12%) have one <i>CYP2C19*2</i> allele and one <i>CYP2C19*1</i> allele (heterozygous). Moreover, 42 (2.96%) were carrying two <i>CYP2C19*17</i> alleles (homozygous), and 262 (18.49%) were carrying one <i>CYP2C19*17</i> allele and one wild-type allele of <i>CYP2C19</i> (heterozygous). The most common <i>CYP2C19</i> genotypes reported among Arabs was the wild-type <i>*1/*1</i>, of which 49.26% of them had the homozygous form of the <i>CYP2C19*1</i> allele. The frequency of the CYP2C19*1 allele was 71.07%, followed by the <i>CYP2C19*2</i> allele (16.73%) and <i>CYP2C19*17</i> (12.21%), respectively. The <i>CYP2C19*3</i> allele was detected rarely among Arabs (&lt;1%) compared to <i>CYP2C19*1, *2</i>, and <i>*17</i> alleles. The present study revealed that Arabs carrying <i>CYP2C19*2</i> and <i>CYP2C19*3</i> alleles may not respond to clopidogrel and may put those patients at risk of recurrent CVEs. Carriers of the <i>CYP2C19*17</i> allele, on the other hand, did not show a significant role either in increasing or decreasing the antiplatelet efficacy of clopidogrel. The <i>CYP2C19</i> genotypes including <i>*1/*1, *1/*2, *1/*17, *2/*2</i>, and <i>*17/*17</i> are commonly distributed among the Arabs.