CYP2C19 Genetic Polymorphism in Saudi Arabians

Abstract

Abstract:The main objective of this study was to evaluate CYP2C19 genetic polymorphism in a Saudi Arabian population by determining the frequencies of CYP2C19*2, *3, *4, *6, *7 and *17 alleles and their relevant genotypes. Genomic DNA was isolated from 192 healthy Saudi Arabians, representing different geographical regions, and genotyping of the selected CYP2C19 variants was carried out by direct sequencing after PCR amplification. The allelic frequency of heterozygous CYP2C19*2 was 8.2% with only one individual found to carry the homozygous genotype of this defective allele. None of the other investigated poor metabolizer alleles (i.e. CYP2C19*3, *4, *6 and *7) was detected in the study population. About 46% of the examined volunteers were found to carry CYP2C19*17 genotype (37.5% heterozygous and 8.1% homozygous of the defective allele) with an overall CYP2C19*17 allelic frequency of 26.9%. In addition, a novel CYP2C19 SNP (G356A) and another very rare SNP (C336T) have been identified in this study with a frequency of about 50% for each. Further studies are required to evaluate the metabolic and clinical relevance of CYP2C19*17, G356A and C336T in the Saudi Arabian population.

Genotyping of CYP2C19 polymorphisms and its clinical validation in the ethnic Arab population

“…It should also be mentioned that the distribution of this SNP varies worldwide among the different ethnic groups (http://onlinelibrary.wiley.com/doi/10.1111/jphp.12391/suppinfo, Table ) [29–41]. Interestingly, our observation is similar to recent studies in the same population[24,25] and to those described in the Nordic,[42] German,[43] Greek[44] and Polish[45] populations, but is somewhat at odds with findings in other (Asian) ethnic populations, such as the Chinese,[45] Japanese[46] or Koreans[47] which display a rather low prevalence of the variant. This finding of its low frequency has in fact led to the suggestion that CYP2C19*17 may be of limited clinical use for drugs with very narrow therapeutic indices [48].…”

“…However, the robustness of such platforms still needs to be tested and validated. Furthermore, to date, the phenotypic expression of the CYP2C19 has been established primarily in Europeans[20] and to a much less extent in other ethnic populations, particularly in Arabs, in which only three studies involving small population sizes have thus far been documented [23–25]. Therefore, the aims of this study were to procure exhaustive information on the profiles of CYP2C19 variants in Saudi Arabs and simultaneously test the applicability of two currently available platforms, the DMET Plus microarraying platform and the Luminex x_Tag assay, both designed to routinely genotype individuals in personalized medicine.…”

Analysis of CYP2C19 Genetic Polymorphism in a Large Ethnic Hakka Population in Southern China

“…Recent data demonstrate significant alteration in the enzyme activity result in variable drug responses and increased rates of thrombotic events in patients harboring hepatic cytochrome gene variants [ 10 , 17 – 19 ]. CYP2C19*2 and CYP2C19*3 alleles, which result in the aberrant splicing and a premature stop codon, respectively, have been extensively studied in populations of different ethnicities and geographic origin [ 20 – 23 ]. Since CYP2C19*2 and *3 cover >90% of the poor metabolism population, the mutation genotype contained *1/*2, *1/*3, *2/*2, *2/*3, and *3/*3.…”

Prevalence of CYP2C19 alleles, pharmacokinetic and pharmacodynamic variation of clopidogrel and prasugrel in Bangladeshi population

“…The prevalence of CYP2C19*2 and CYP2C19*17 in Bangladesh is different from any other race as compared with the HapMap‐CEU, HapMap‐YRI, HapMap‐JPT, and HapMap‐CHB groups of European, African and Asian ancestry. The estimated allele frequency of the LOF allele, CYP2C19*2 and GOF allele, CYP2C19*17 is high in comparison to all races except Greek and Saudi Arabian . To the best of our knowledge, this is the first study comparing the genotypic distribution of CYP2C19*2 and CYP2C19*17 between healthy and patients undergoing PCI taking clopidogrel.…”