Abstract
Purpose: To investigate the influence of allelic frequencies of PON1 Q192R, CYP2C19*2 and CYP2C19*17 genetic polymorphisms on the response to clopidogrel among Jordanian patients. Methods: Polymorphisms in CYP2C19 were assessed among 148 patients using PCR-RFLP assay. Results: The CYP2C19*2, CYP2C19*17, and PON1 Q192R allele frequencies were 9.8, 28.72 and 28.7 %, respectively. On the genotyping side, the frequencies of CYP2C19*1/1* and CYP2C19*1/2* were 80.4 and 19.6 %, respectively, but none of the patients had CYP2C19*2/2* genotype. The genotype frequencies CYP2C19*17 were 47.97, 46.62 and 5.41 % for wild-type C-C, heterozygote C-T, and the mutant T-T, respectively. PON1 genotype was 42.7 % for QQ, and 57.8 % for QR. None of the patients had RR genotype. Conclusion: Relative to other populations, the observed allelic frequencies are consistent with the values reported for Caucasian and Middle Eastern populations. Keywords: CYP2C9 polymorphisms, Clopidogrel, Genotype, Allele frequency, PON1 genes
Highlights
Cytochrome 2C19 (CYP2C19) i s responsible for the metabolism of many drugs such as smephenytoin, proton pump inhibitors (PPIs), clopidogrel and proguanil [1]
The present study was carried out to determine the allelic frequency of PON1 Q192R, CYP2C19*2, and CYP2C19*17 among Jordanian patients on clopidogrel therapy
The CYP2C19*17 allele and genotype frequencies reported in this study indicate that a substantial percentage of Jordanians have increased activity of the CYP2C19 enzyme
Summary
Cytochrome 2C19 (CYP2C19) i s responsible for the metabolism of many drugs such as smephenytoin, proton pump inhibitors (PPIs), clopidogrel and proguanil [1]. The most frequent SNPs are CYP2C19*2 and CYP2C19*3 which cause complete absence of enzymatic activity in vitro and in vivo [ 3 ] Another common alteration that results in multiple active alleles leading to increased activity of the enzyme is CYP2C19*17 [3]. Many studies have reported that PM patients who have CYP2C19*2 loss-of-function allele are associated with marked decrease in platelet response to clopidogrel, and increased cardiovascular events [4]. PON1 is the f i r st enzyme thatcatalyzes the second stage in clopidogrel bio-activation process [6] These observations are consistent with the observed decreases in plasma paraoxonase activity, the maximum concentrations of active clopidogrel metabolites, and the increases in percentage of platelet inhibition in patients with QQ genotype. The present study was carried out to determine the allelic frequency of PON1 Q192R, CYP2C19*2, and CYP2C19*17 among Jordanian patients on clopidogrel therapy. Levels were deemed significant at p values less than 0.05
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