Genotyping of CYP2C19 polymorphisms and its clinical validation in the ethnic Arab population. (14th February 2015)

• Record Type: Journal Article
• Authors: Tayeb, Hamsa T.; Bakheet, Dana H.; Zaza, Khaled; Wakil, Salma M.; Dzimiri, Nduna
• Is Part Of: Journal of pharmacy and pharmacology. Volume 67:Number 7(2015:Jul.)
• Page Start: 972
• Page End: 979
• Publication Date: 2015-02-14
• Subjects: Pharmacy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/jphp.12391
• Languages: English
• ISSNs: 0022-3573

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="jphp12391-sec-0001" sec-type="section"> <title>Objectives</title> <p>The drug‐metabolizing enzymes and transporters (DMET) Plus microarray and x‐Tag assays have recently been developed for genotyping individuals in personalized medicine. Furthermore, the cytochrome 450‐2C19 (CYP2C19) is a key metabolic enzyme encoded by a polymorphic gene commonly associated with diminished metabolism and variable clinical responses to several drugs in an ethnicity‐dependent fashion. Therefore, validation of these clinical procedures as well as knowledge of the ethnic‐specific incidences of these gene variants is prerequisite for determining their clinical relevance in any given population.</p> </sec> <sec id="jphp12391-sec-0002" sec-type="section"> <title>Methods</title> <p>We determined the distribution of familiar CYP2C19 variants by the DMET Plus chip in 600 candidates and replicated the findings by the Affymetrix Axiom Genome‐Wide Asian Structure Identification Array in 5413 individuals, all Saudis of ethic Arab origin. We then tested the robustness of employing the Luminex xMAP system clinically by comparing the results of genotyping 500 Saudi individuals visiting the Blood Bank of our institution with the findings of the two platforms.</p> </sec> <sec id="jphp12391-sec-0003" sec-type="section"> <title>Key findings</title> <p>The DMET Plus genotyping revealed that eight of the CYP2C19 variants showed some changes. Thereby, the <italic>CYP</italic><italic>2</italic><italic>C</italic><italic>19*17</italic> exhibited the highest minor allele frequency (MAF) of 0.256, followed by the CYP2C19_801 (frequency = 0.055). Six other variants, including the CYP2C19*3, showed MAF in the range of 0.001–0.002. We replicated the frequencies of the <italic>CYP</italic><italic>2</italic><italic>C</italic><italic>19*17</italic> and CYP2C19*3, and additionally established that of the CYP2C19*2 (0.099) using the Axiom platform. The xTag genotyping also indicated that 0.834 of the 500 Saudi individuals were extensive metabolizers (*1/*1), 0.158 carried the *1/*2 genotype, 0.01% carried *2/*2 (poor metabolizers) and one each (0.2%) harboured the *1/*8, *2/*3 (intermediate metabolizers) and *8/*8 (poor metabolizers) genotypes.</p> </sec> <sec id="jphp12391-sec-0004" sec-type="section"> <title>Conclusions</title> <p>The results showed reproducible genotyping of the CYP2C19 variants in the Saudi Arab population using two Affymetrix platforms and phenotyping using the Luminex xTag assay. The prevalence of two clinically relevant genotypes (<italic>CYP</italic><italic>2</italic><italic>C</italic><italic>19*2</italic> and <italic>CYP</italic><italic>2</italic><italic>C</italic><italic>19*3</italic>) were similar to other ethnic groups, while that of the <italic>CYP</italic><italic>2</italic><italic>C</italic><italic>19*17</italic> was comparably higher.</p> </sec> </abstract>