• Expert Opin Drug Metab Toxicol · Mar 2012

    Review

    Cytochrome P450 variations in different ethnic populations.

    • Joseph McGraw and Donald Waller.
    • Concordia University Wisconsin, School of Pharmacy, 12800 N. Lakeshore Drive, Mequon, WI 53022, USA. Joseph.mcgraw@cuw.edu
    • Expert Opin Drug Metab Toxicol. 2012 Mar 1;8(3):371-82.

    IntroductionVariability of drug response is an important consideration in clinical medicine. A major determinant of drug response variability is hepatic cytochrome P450 oxidase (CYP450)-mediated drug metabolism. Advances in genetics permits genotyping large numbers of patients to identify single nucleotide polymorphisms (SNPs) which may result in variant CYP450 enzyme expression and/or activity. New SNPs with functional impacts are constantly being identified which further explain variability in CYP450 phenotype.Areas CoveredThe racial/ethnic distribution of selected CYP450 (CYP1A2, P2C8/9/19, 2D6 and 3A4/5) SNPs are reviewed with an emphasis on the agreement between genotype and phenotype. The reader will gain insight into the SNP distribution by racial/ethnic group and the corresponding relationship between important, highly prevalent, SNPs and their impact on metabolic phenotype.Expert OpinionRacial/ethnic differences in metabolic phenotype can be explained by differences in SNP distribution. However, overlap in substrate specificity, linkage disequilibrium and previously unidentified SNPs have made phenotypic characterization difficult for CYP3A4/5 and 2C8/9. Studies utilizing newly identified, highly prevalent, racially stratified SNPs and their impact on CYP isoform-specific metabolism will provide new answers.

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