Cytochrome P450 variations in different ethnic populations

Expert Opin Drug Metab Toxicol. 2012 Mar;8(3):371-82. doi: 10.1517/17425255.2012.657626. Epub 2012 Jan 31.

Abstract

Introduction: Variability 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 covered: The 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 opinion: Racial/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.

Publication types

  • Review

MeSH terms

  • Biotransformation
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / metabolism
  • Ethnic Groups / genetics*
  • Gene Frequency
  • Genotype
  • Humans
  • Liver / enzymology*
  • Pharmacogenetics
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Xenobiotics / metabolism

Substances

  • Xenobiotics
  • Cytochrome P-450 Enzyme System