title: Genotyping of human cytochrome P450 2A6 (CYP2A6), a nicotine C-oxidase.
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.
authors.affiliation: Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Oscarson
authors.forename: H
authors.initials: H
authors.lastname: Gullstén
authors.forename: A
authors.initials: A
authors.lastname: Rautio
authors.forename: M L
authors.initials: ML
authors.lastname: Bernal
authors.forename: B
authors.initials: B
authors.lastname: Sinues
authors.forename: M L
authors.initials: ML
authors.lastname: Dahl
authors.forename: J H
authors.initials: JH
authors.lastname: Stengård
authors.forename: O
authors.initials: O
authors.lastname: Pelkonen
authors.forename: H
authors.initials: H
authors.lastname: Raunio
authors.forename: M
authors.initials: M
authors.lastname: Ingelman-Sundberg
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics; D005006:Ethnicity; D005387:Finland; D005838:Genotype; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012907:Smoking / Q000235:genetics*; D013030:Spain; D013548:Sweden; D014029:Tobacco Use Disorder / Q000201:enzymology / Q000235:genetics; D044465:White People / Q000235:genetics*
chemical_list: D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; C034523:nicotine oxidase