Abstract
Purpose: To investigate the association of *2 and *17 single nucleotide polymorphisms (SNPs) of CYP2C19 gene with hypertension in Pakistani population.
 Methods: The study was conducted on 527 hypertensive patients and 530 unrelated healthy controls from selected regions of Pakistan. DNA was extracted from leukocytes and all patients and controls were genotyped for two SNPs (rs4244285 and rs12248560) of CYP2C19 gene by allele specific polymerase chain reaction (AS-PCR).
 Results: Multi-allelic polymorphism in CYP2C19 identified four distinct phenotypes known as ultra-rapid metabolizer (UM), extensive metabolizer (EM), intermediate metabolizer (IM) and poor metabolizer (PM) in hypertensive patients and controls. For CYP2C19*2 polymorphisms, overall wild type and mutant allele frequency were 75 and 25 % in hypertensive patients, and 64.2 and 35.8 % in controls. For CYP2C19*17 polymorphisms, the overall wild type and mutant allele frequency were 66.6 and 33.4 % in hypertensive patients and 75.6 % and 24.4 % in controls. Significant difference in allele frequencies for CYP2C19*2 and *17 was demonstrated between hypertensive and non-hypertensive subjects.
 Conclusion: To the best of our knowledge, this is the first report on CYP2C19 frequencies in hypertensive Pakistani patients. The finds should help clinicians to determine a suitable optimal dosage of some drugs in order to reduce side effects.
Highlights
Cytochrome P450 2C19 (CYP2C19), an important enzyme of the cytochrome P450 family, is involved in the metabolism of several drugs
The study was conducted in compliance with the Declaration of Helsinki [9] and was approved by the Ethical Committee and Institutional Review Board (IRB) of Quaid-i-Azam University, Islamabad (#IRB-QAU-97)
CYP2C19 alleles CYP2C19*2 (c.G681A; rs4244285) and CYP2C19*17 (c.C806T; rs12248560) were genotyped by Allele-specific (AS-PCR) and the primer data is given in supplementary data (Table 2 and 3)
Summary
Cytochrome P450 2C19 (CYP2C19), an important enzyme of the cytochrome P450 family, is involved in the metabolism of several drugs. Psychiatric patients having CYP2C19*17 allele show 42 % lower escitalopram serum levels showing high risk of treatment failure [3]. Another study reported that PM of CYP2C19 had higher levels of Gliclazide suggesting CYP2C19 role in Gliclazide clearance [6]. CYP2C19 PM genotype in cirrhotic patients having hepatitis C virus is associated with higher risk of developing hepatocellular carcinoma [7]. Previous studies revealed that CYP2C19 rs10509676 variant homozygote (AA genotype) was associated with HTN [8]. The present study was carried out to explore the association of *2 and *17 alleles of CYP2C19 and HTN and how it’s affecting recent treatment regimes. Association between the CYP2C19*2 and CYP2C19*17 variants and HTN was determined using SPSS version 20.0 [10]. Chi-square test was used to test the significance of the Hardy-Weinberg equilibrium of the polymorphism of the two genes in the entire data of the patient and the control groups
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