INTERINDIVIDUAL DIFFERENCES IN NICOTINE METABOLISM AND GENETIC POLYMORPHISMS OF HUMAN CYP2A6

Nicotine is widely consumed throughout the world, and exerts a number of physiological effects. After nicotine is absorbed through the lungs by cigarette smoking, it undergoes extensive metabolism in humans. Nicotine is mainly metabolized to cotinine by cytochrome P450 (CYP) 2A6. CYP2A6 can metaboli...

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Published inDrug metabolism reviews Vol. 34; no. 4; pp. 865 - 877
Main Authors Nakajima, Miki, Kuroiwa, Yukio, Yokoi, Tsuyoshi
Format Journal Article
LanguageEnglish
Published New York, NY Informa UK Ltd 01.01.2002
Taylor & Francis
Informa Healthcare
Subjects
Animals
Area Under Curve
Aryl Hydrocarbon Hydroxylases - genetics
Aryl Hydrocarbon Hydroxylases - metabolism
Biological and medical sciences
Cytochrome P-450 CYP2A6
Cytochrome P450
Ethnic difference
Genetic Polymorphism
Humans
Interindividual difference
Medical sciences
Mixed Function Oxygenases - genetics
Mixed Function Oxygenases - metabolism
Nicotine - blood
Nicotine - metabolism
Polymorphism, Genetic - physiology
Tobacco, tobacco smoking
Toxicology
Alkaloid
Tobacco
Toxicity
Cytochrome P450
Interindividual comparison
Risk factor
Drug of abuse
Review
Malignant tumor
Metabolism
Nicotine
Polymorphism
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Summary:Nicotine is widely consumed throughout the world, and exerts a number of physiological effects. After nicotine is absorbed through the lungs by cigarette smoking, it undergoes extensive metabolism in humans. Nicotine is mainly metabolized to cotinine by cytochrome P450 (CYP) 2A6. CYP2A6 can metabolize some pharmaceutical agents such as halothane, valproic acid, and fadrozole, and activate tobacco-specific nitrosamines. There are large interindividual differences in nicotine metabolism, and it has been found that the interindividual differences are attributed to the genetic polymorphisms of CYP2A6 gene. This review describes the techniques for determination of in vivo nicotine metabolism, characteristics of each human CYP2A6 alleles, and ethnic differences. The relationship between CYP2A6 genetic polymorphism and potency of nicotine metabolism, smoking behavior, and cancer risk are extensively reviewed. Finally, the usefulness of nicotine metabolism for phenotyping of CYP2A6 in individuals and implication of the significance of CYP2A6 genetic polymorphism in a clinical perspective are discussed.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
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ObjectType-Review-1
ISSN:0360-2532
1097-9883
DOI:10.1081/DMR-120015696