Validation of methods for CYP2C9 genotyping: frequencies of mutant alleles in a Swedish population

Biochem Biophys Res Commun. 1999 Jan 27;254(3):628-31. doi: 10.1006/bbrc.1998.9992.

Abstract

Cytochrome P450 2C9 (CYP2C9) catalysis the metabolism of important drugs such as phenytoin, S-warfarin, tolbutamide, losartan, torasemide, and nonsteroidal anti-inflammatory drugs. A functional polymorphism of the CYP2C9 gene has been described. The variant alleles include CYP2C9*2 having a point mutation in exon 3 causing an Arg144Cys exchange, and CYP2C9*3 with a point mutation in exon 7 resulting in an Ile359Leu exchange. Genotyping of these variant forms was carried out in 430 Swedish healthy volunteers and three different methods were compared. Sequence analysis of the different PCR products revealed that other genes in the CYP2C locus were co-amplified in one of the methods applied, whereas the other two methods were specific for CYP2C9. The frequencies of the CYP2C9*1, CYP2C9*2 and CYP2C9*3 alleles in the population examined were found to be 0.819, 0.107, and 0.074, respectively. The need for careful evaluation of the genotyping procedure by sequence analysis of PCR products is emphasised.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles*
  • Aryl Hydrocarbon Hydroxylases*
  • Cytochrome P-450 CYP2C9
  • Cytochrome P-450 Enzyme System / genetics*
  • Female
  • Gene Frequency*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Steroid 16-alpha-Hydroxylase*
  • Steroid Hydroxylases / genetics*
  • Sweden / ethnology

Substances

  • Cytochrome P-450 Enzyme System
  • Steroid Hydroxylases
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • Steroid 16-alpha-Hydroxylase