title: Deficient cotinine formation from nicotine is attributed to the whole deletion of the CYP2A6 gene in humans.
abstract: Nicotine is mainly metabolized to cotinine by cytochrome P450 (CYP) 2A6. Large interindividual differences in nicotine metabolism have been reported in humans. The purpose of this study was to clarify the relationship between the poor metabolism of nicotine and the existence of the CgammaP2A6v1 and CgammaP2A6v2 alleles, and a whole deletion allele of the CgammaP2A6 gene. The plasma concentrations of nicotine and cotinine were measured in 10 healthy subjects after each smoked one cigarette or chewed one piece of nicotine gum. One subject showed no detectable cotinine level in plasma when smoking and the lowest cotinine level when receiving nicotine gum. The subject was regarded as a poor metabolizer of nicotine by a probit analysis and was found to carry a homozygous whole deletion allele of the CgammaP2A6 gene. This is the first report to show that deficient cotinine formation in humans is attributed to the whole deletion of the CgammaP2A6 gene.
authors.affiliation: Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nakajima
authors.forename: S
authors.initials: S
authors.lastname: Yamagishi
authors.forename: H
authors.initials: H
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Kuroiwa
authors.forename: T
authors.initials: T
authors.lastname: Yokoi
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases; D003367:Cotinine / Q000097:blood / Q000378:metabolism*; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009538:Nicotine / Q000097:blood / Q000378:metabolism*; D018722:Nicotinic Agonists / Q000097:blood / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012016:Reference Values; D017422:Sequence Analysis, DNA; D012907:Smoking / Q000097:blood / Q000378:metabolism*
chemical_list: D018722:Nicotinic Agonists; D009538:Nicotine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; D003367:Cotinine