Screening for CYP2C19 Gene variants in a healthy Jordanian population

Salem Yasin,Reem Abdellatif,Lubna Tahtamouni,Rema Al-Khateeb,Al-Hakam Al-Hadidi,Hakam Al-Khateeb,Ala'A Al-Emerieen,Zainab Al-Mazaydeh

doi:10.4314/tjpr.v15i12.30

Abstract

Purpose: To genotype healthy Jordanian population from three different provinces (Amman, Zarqa and Irbid) for cytochrome P4502C19 and to identify the allelic distribution of CYP2C19 variants in comparison with other findings around the world. Methods: Healthy Jordanian volunteers were recruited from government hospitals. Two hundred and sixty volunteers were included in the study regardless of sex and age. CYP2C19*2, *3,*4, *5, and *6 alleles were studied using polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) technique. Results: The results show that the Jordanian population tested exhibited 9 genotypes out of the 21 expected CYP2C19 genotypes. CYP2C19*1/*1 and *2/*2 genotypes were the most prominent in the sample population, while CYP2C19*2/*5 was the least prevalent genotype. The frequencies of the CYP2C19 variants did not deviate from Hardy-Weinberg equilibrium. Allele frequency of CYP2C19*2 in the Jordanian population was statistically different from that found in most Europeans, North and South Americans, Africans, and some Asian ethnic communities but not with South-East Asian populations (China, Chinese-Taiwanese, and Philippines) and Australian Aborigines. Conclusion: The findings of this study confirm the importance of CYP2C19 genotyping prior to drug therapy administration to achieve optimal dosage and cost-effective therapy. Keywords: Cytochrome P450, RFLP-PCR, Allele frequency, Pharmacogenetics, Optimal dosage, Costeffective therapy

Highlights

Individual variation in response to drugs is a substantial clinical problem that can be inherited
Polymorphisms of genes encoding drug metabolism enzymes, drug transporters, and drug receptors, which are involved in drug responses, have been reported [3,4]
As the main cause of the variation in drug response, attention has focused on genetic polymorphisms

Summary

Introduction

Individual variation in response to drugs is a substantial clinical problem that can be inherited. The genetically determined variability in drug response defines the research area known as pharmacogenetics [1]. One of the main directions in development of pharmacogenetics is identifying genes and allelic variants of genes that affect human's response to drugs [2]. Genetic variation can account for as much as 95 % of variability in drug disposition and effect [5]. As the main cause of the variation in drug response, attention has focused on genetic polymorphisms. Single nucleotide polymorphism (SNP) of DNA produces variation in drug response and has become a representative research target in pharmacogenetics [6]

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Conclusion