CYP2C9, CYPC19 and CYP2D6 gene profiles and gene susceptibility to drug response and toxicity in Turkish population

Abstract

Pharmacogenetics is a vast field covering drug discovery research, the genetic basis of pharmacokinetics and dynamics, genetic testing and clinical management in diseases. Pharmacogenetic approach usually focuses on variations of drug transporters, drug targets, drug metabolizing enzymes and other biomarker genes. Cytochrome P450 (CYP) enzymes, an essential source of variability in drug-response, play role in not only phase I-dependent metabolism of xenobiotics but also metabolism of endogenous compounds such as steroids, vitamins and fatty acids. CYP2C9, CYP2C19 and CYP2D6 enzymes being highly polymorphic are responsible for metabolism of a variety of drug groups. In the study, it was determined the genotype and allele frequency of CYP2C9*2, CYP2C19*3, CYP2C19*2, CYP2C19*3, CYP2C19*17, CYP2D6*9 and CYP2D6*41, very common and functional single-nucleotide polymorphisms (SNPs), in healthy volunteers. The genotype distributions were consistent with the Hardy-Weinberg equilibrium in the population (p> 0.05). It is believed that the determination of polymorphisms in the enzymes may be beneficial in order to prevention or reduction in adverse effects and death. The recessive allele frequencies of CYP2C9*2, CYP2C19*3, CYP2C19*2, CYP2C19*3, CYP2C19*17, CYP2D6*9 and CYP2D6*41 were 11, 13, 12, 13, 25, 4 and 15%, respectively. According to the obtained results, the carriers of CYP2D6*9 variant allele should be received higher doses of the drugs metabolizing with this enzyme in Turkish population, while the carriers of other variant alleles do not generally have any requirement of dose regimen. (C) 2016 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University.