Allele Frequency Distribution of CYP2C19*3 and CYP1A1 Allelic Variants Associated with Clopidogrel Resistance in Cardiac Patients of Pakistan
Allele Frequency Distribution of CYP2C19*3 and CYP1A1 Allelic Variants Associated with Clopidogrel Resistance in Cardiac Patients of Pakistan
Kashif-ur-Rehman1,2, Ahmad Bakhsh1, Muhammad Akram Tariq3,
Muhammad Khalil Ahmad Khan4 and Sumaira Mehboob1*
ABSTRACT
Drug resistance is a phenomenon that has received serious attention nowadays in medical practice. Such is the case with clopidogrel treatment response, which is variable inter-individually and inter-ethnically due to genetic polymorphisms in Cytochrome P450 (CYP) gene. Clopidogrel is an anti-platelet agent administered to cardiac patients in the form of a prodrug, which is further metabolized into an active form by the CYP enzymes. There are many allelic variants of the CYP gene which are involved in clopidogrel resistance but CYP2C19*3 has been proven one of the most significant loss-of-function alleles and the role of CYP1A1 has also been determined in reduced response to clopidogrel. We selected 100 cardiac patients with PCI or ACS who were on clopidogrel treatment and analyzed them for CYP2C19*3 and CYP1A1 allelic variants using gel-based screening of allele-specific amplified products. Sanger sequencing was utilized for the validation of our gel-based genotypes. The observed allelic frequency distribution of CYP2C19*3 variants were 35% heterozygous for A/G variants, 12% homozygous for A variant, and 53% homozygous for G wild type. While in the case of CYP1A1, the allelic frequency distribution of its variants were 5% heterozygous for A/C/G variants, 9% heterozygous for A/G variants, 7% heterozygous for A/C variants, and 79% homozygous for A/A wild type. The overall frequency of CYP1A1 G variants was 14% and C variants were 12%. Our results suggested that there are significant inter-ethnic variations in the allelic frequencies of CYP2C19*3 and CYP1A1 which may be responsible for variable clopidogrel treatment response in Pakistani cardiac patients.
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