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Titolo:
Relationship between interindividual differences in nicotine metabolism and CYP2A6 genetic polymorphism in humans
Autore:
Nakajima, M; Kwon, JT; Tanaka, N; Zenta, T; Yamamoto, Y; Yamamoto, H; Yamazaki, H; Yamamoto, T; Kuroiwa, Y; Yokoi, T;
Indirizzi:
Kanazawa Univ, Fac Pharmaceut Sci, Div Drug Metab, Kanazawa, Ishikawa 9200934, Japan Kanazawa Univ Kanazawa Ishikawa Japan 9200934 wa, Ishikawa 9200934, Japan Kanazawa Univ, Sch Med, Dept Biochem, Kanazawa, Ishikawa 9200934, Japan Kanazawa Univ Kanazawa Ishikawa Japan 9200934 wa, Ishikawa 9200934, Japan Showa Univ, Sch Pharmaceut Sci, Dept Clin Pharm, Tokyo 142, Japan Showa Univ Tokyo Japan 142 maceut Sci, Dept Clin Pharm, Tokyo 142, Japan
Titolo Testata:
CLINICAL PHARMACOLOGY & THERAPEUTICS
fascicolo: 1, volume: 69, anno: 2001,
pagine: 72 - 78
SICI:
0009-9236(200101)69:1<72:RBIDIN>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN LIVER-MICROSOMES; COUMARIN 7-HYDROXYLATION; C-OXIDATION; DELETION; SMOKING; IDENTIFICATION; FREQUENCY; CANCER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Nakajima, M Kanazawa Univ, Fac Pharmaceut Sci, Div Drug Metab, Takara Machi 13-1, Kanazawa, Ishikawa 9200934, Japan Kanazawa Univ Takara Machi 13-1 Kanazawa Ishikawa Japan 9200934
Citazione:
M. Nakajima et al., "Relationship between interindividual differences in nicotine metabolism and CYP2A6 genetic polymorphism in humans", CLIN PHARM, 69(1), 2001, pp. 72-78

Abstract

Background: Nicotine is mainly metabolized to cotinine by cytochrome P450 (CYP) 2A6. Previously, we found that the CYP2A6 gene was deleted homozygously in one subject who was deficient in cotinine formation from nicotine. Objective: Our objective was to clarify the relationship between interindividual differences in nicotine metabolism and CYP2A6 genetic polymorphism. Methods: Nicotine was administered to 92 healthy Japanese subjects in the form of 1 piece of nicotine gum to investigate the potency of nicotine metabolism. The cotinine-nicotine ratio of the plasma concentration 2 hours after chewing was calculated as an index of nicotine metabolism. The genotypesof CYP2A6 gene, CYP2A6*1A, CYP2A6*1B, CYP2A6*2, CYP2A6*3, CYP2A6*4, and CYP2A6*5, were determined with polymerase chain reaction-restriction fragmentlength polymorphism. Results: A large interindividual difference in nicotine metabolism was observed. Allele frequencies of CYP2A6*1A, CYP2A6*1B, and CYP2A6*4 were 42.4%,37.5%, and 20.1%, respectively. The CYP2A6*2, CYP2A6*3, and CYP2A6*5 alleles were not found. Three subjects genotyped as CYP2A6*4/CYP2A6*4 were completely deficient in cotinine formation. The heterozygotes of the CYP2A6*4 allele tend to show lower capacities for cotinine formation. The subjects with CY2A6*1A/CY2A61B appeared to have higher capacities of cotinine formationthan subjects with CY2A6*1/CYP2A6*1A, although the difference was not significant. The probit plot of the cotinine-nicotine ratio was not linear; this possibly indicated the existence of a novel mutation in the CYP2A6 gene genotyped as CYP2A6*1B/CYP2A6*4. Conclusions: The relationship between interindividual differences in nicotine metabolism and CYP2A6 genetic polymorphism in humans was proved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/07/20 alle ore 05:35:47