GENOTYPING OF HUMAN CYTOCHROME-P450 2A6 (CYP2A6), A NICOTINE C-OXIDASE

Cytochrome P450 2A6 (CYP2A6) is a polymorphic enzyme responsible for t he oxidation of certain precarcinogens and drugs and is the major nico tine C-oxidase, The role of CYP2A6 for nicotine elimination was emphas ised recently by the finding that smokers carrying defective CYP2A6 al leles consumed fewer cigarettes [Pianezza et al, (1998) Nature 393, 75 0]. The method used for CYP2A6 genotyping has, however, been found to give erroneous results with respect to the coumarin hydroxylase phenot ype, a probe reaction for the CYP2A6 enzyme. The present study describ es an allele-specific PCR genotyping method that identifies the major defective CYP2A6 allele and accurately predicts the phenotype, An alle le frequency of 1-3% was observed in Finnish, Spanish, and Swedish pop ulations, much lower than described previously. (C) 1998 Federation of European Biochemical Societies.