1887

Abstract

Background Clopidogrel is used by around 40 million patients worldwide to treat and prevent thrombotic events. Third of the patients have clopidogrel resistance which may lead to treatment failure. cytochrome P450 (CYP450) 2C19 enzyme (CYP2C19) is one of the key enzymes involved in the hepatic bio-activation of clopidogrel. Several studies have shown that polymorphisms in the gene encoding the CYP2C19 contribute to variability in response to clopidogrel. There is no available data on the distribution of CYP2C19 genetic polymorphisms in the Qatari population. Objective The objective of this study was to estimate the distribution of CYP2C19 genetic polymorphisms in Qatari population by determining the prevalence of CYP2C19*2, *3 and *17 alleles. Methods The study was conducted on a cohort of 129 adult Qatari individuals. DNA was extracted mainly from saliva samples by Oragene® self-collection kit and purified using the prepIT™√L2P purification protocol (DNA Genotek, Inc., Canada). For those who were unable to provide saliva, blood sample was collected. Five milliliters of peripheral blood were collected in test tubes containing EDTA and DNA was extracted using PureLink® genomic DNA extraction kit for purification of genomic DNA (Invitrogen life technologies, Germany). The amount and purity of the DNA samples were quantified using Nanodrop 2000 Spectrophotometer (Thermo Scientific, Wilmington, DE, USA). Genotyping was performed for CYP2C19*2 (rs4244285), CYP2C19*3 (rs4986893), and CYP2C19*17 (rs12248560) using Fast 7500 Real-Time PCR System (Applied Biosystems™, USA) with TaqMan assays according to the manufacturer's instructions. Genotype frequencies were tested for deviations from Hardy–Weinberg equilibrium through chi-square analysis at P value of 0.05. Patients were categorized according to their CYP2C19 genotype into: ultra-rapid (*1/*17, *17/*17); extensive (*1/*1); intermediate (*1/*2, *1/*3, *2/*17); poor (*2/*2, *2/*3, *3/*3) metabolizers. Results This study included 129 Qatari individuals. Majority of our patients were 50 years and above (60%) and mostly females (63%). The allele frequencies were CYP2C19*1 (86 %), *2 (4%), *3 (0%) and *17 (10%). Fifty-eight subjects (45%) were homozygous for the *1/*1 genotype. Heterozygous genotypes were identified in 62 patients (48.1%), 42 carrying *1/*17 (32.6%), 12 carrying CYP2C19 *1/*2 (9.3%), and 8 carrying CYP2C19 *2/*17 (6.2%). Six patients were homozygous for the gain-of-function allele, CYP2C19 *17/*17 (4.7%). On the other hand, three patients were homozygous for the loss-of-function allele, CYP2C19 *2/*2 (2.3%). However, no subject was found to have *3 allele. All the genotypes were in Hardy–Weinberg equilibrium. The distribution of CYP2C19 phenotypes was divided into extensive metabolizers (*1/*1) (45%), ultra-rapid metabolizers (*1/*17, *17/*17) (37.2%), intermediate metabolizers (*1/*2, *1/*3, *2/*17) (15.5%), and poor metabolizers (*2/*2) (2.3%). Conclusion To the best of our knowledge, this is the first study to report the distribution of CP2C19 genetic polymorphisms in Qatari population. These findings have important clinical implications for the use of clopidogrel and other medications affected by CYP2C19 mutations in Qatari population. Thus, future association studies are needed to reveal clinical consequence of these genetic polymorphisms in Qataris.

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/content/papers/10.5339/qfarc.2018.HBPD660
2018-03-15
2020-11-30
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http://instance.metastore.ingenta.com/content/papers/10.5339/qfarc.2018.HBPD660
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