Study frequency of CYP2C19*2 (rs4244285) and *3 (rs4986893 ) genetic variants and their response to Clopidogrel in a healthy Iranian population

extensive genome studies have revealed that single nucleotide polymorphisms (SNP) will be there among individuals, which directly and indirectly affects the expression of the gene and causes the disease. So, these SNPs are useful for pharmacogenomics studies and risk Assessment to illness. Clopidogrel (Plavix) is a platelet inhibitor used to treat cardiovascular diseases. It is often prescribed to prevent ischemic events following acute coronary syndromes, and for patients undergoing percutaneous coronary intervention. and a prodrug that requires transformation into an active metabolite by cytochrome P-450 (CYP) enzymes for its antiplatelet effect. That CYP2C19 plays a major role in clopidogrel metabolism because CYP2C19 contributes in both of the two sequential oxidative metabolic steps of clopidogrel activation. Since the gene encoding CYP2C19 enzyme is polymorphic and its genetic variants are mostly null alleles with reduced function. Several clinical studies have shown that CYP2C19*2 and *3 genetic variants of 2C19 gen reduce active metabolicte and decreased platelet responsiveness among clopidogrel-treated subjects. So, the aim of this study was to investigate the frequencies of CYP2C19*2 and CYP2C19*3 variants in the Iranian population in order to determine their prevalence and their relationship with side effects of clopidogrel. the allelic and genotypic frequency of CYP2C19*2 and CYP2C19*3 was measured using PCR-SSCP, PCR-RFLP in 538 blood samples obtained from healthy volunteers from different parts of Iran. The allelic frequencies of CYP2C19*3 was not observed in the population of Iran whereas the genotypic frequencies of wild-type homozygous (G/G), heterozygous (G/A) and homozygous mutant (A/A) of CYP2C19*2 variants were found 63.8%, 30.1% and 6.1% respectively. These data indicate that clopidogrel side effects are common among the Iranian. and also CYP2C19*2 and *3 have a significant relationship with the decrease of the active metabolite of clopidogrel, diminished platelet inhibition, and a higher rate of major adverse cardiovascular events, including myocardial infarction and stent thrombosis.

Keywords:

pharmacogenetics , polymorphism , cytochrome P450 genes , healthy population of Iran , Clopidogrel