Genotyping of human cytochrome P450 2A6 (CYP2A6), a nicotine C-oxidase

FEBS Lett. 1998 Nov 6;438(3):201-5. doi: 10.1016/s0014-5793(98)01297-6.

Abstract

Cytochrome P450 2A6 (CYP2A6) is a polymorphic enzyme responsible for the oxidation of certain precarcinogens and drugs and is the major nicotine C-oxidase. The role of CYP2A6 for nicotine elimination was emphasised recently by the finding that smokers carrying defective CYP2A6 alleles consumed fewer cigarettes [Pianezza et al. (1998) Nature 393, 750]. The method used for CYP2A6 genotyping has, however, been found to give erroneous results with respect to the coumarin hydroxylase phenotype, a probe reaction for the CYP2A6 enzyme. The present study describes an allele-specific PCR genotyping method that identifies the major defective CYP2A6 allele and accurately predicts the phenotype. An allele frequency of 1-3% was observed in Finnish, Spanish, and Swedish populations, much lower than described previously.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aryl Hydrocarbon Hydroxylases*
  • Cytochrome P-450 CYP2A6
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / metabolism
  • Diabetes Mellitus, Type 2 / enzymology
  • Diabetes Mellitus, Type 2 / genetics
  • Ethnic Groups
  • European Continental Ancestry Group / genetics*
  • Finland
  • Genotype
  • Humans
  • Mixed Function Oxygenases / genetics*
  • Mixed Function Oxygenases / metabolism
  • Oxidoreductases / genetics*
  • Oxidoreductases / metabolism
  • Phenotype
  • Polymerase Chain Reaction
  • Smoking / genetics*
  • Spain
  • Sweden
  • Tobacco Use Disorder / enzymology
  • Tobacco Use Disorder / genetics

Substances

  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Oxidoreductases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2A6 protein, human
  • Cytochrome P-450 CYP2A6
  • nicotine oxidase