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Titolo:
Characterisation and PCR-based detection of a CYP2A6 gene deletion found at a high frequency in a Chinese population
Autore:
Oscarson, M; McLellan, RA; Gullsten, H; Yue, QY; Lang, MA; Bernal, ML; Sinues, B; Hirvonen, A; Raunio, H; Pelkonen, O; Ingelman-Sundberg, M;
Indirizzi:
Karolinska,Inst, Natl Inst Environm Med, Div Mol Toxicol, S-17177 Stockholm Karolinska Inst Stockholm Sweden S-17177 Mol Toxicol, S-17177 Stockholm Univ Oulu, Dept Pharmacol & Toxicol, Oulu, Finland Univ Oulu Oulu Finland iv Oulu, Dept Pharmacol & Toxicol, Oulu, Finland Med Prod Agcy, Uppsala, Sweden Med Prod Agcy Uppsala SwedenMed Prod Agcy, Uppsala, Sweden Univ Uppsala, Fac Pharm, Div Biochem, Uppsala, Sweden Univ Uppsala Uppsala Sweden la, Fac Pharm, Div Biochem, Uppsala, Sweden Univ Zaragoza, Dept Pharmacol & Physiol, Zaragoza, Spain Univ Zaragoza Zaragoza Spain Dept Pharmacol & Physiol, Zaragoza, Spain Finnish Inst Occupat Hlth, Dept Ind Hyg & Toxicol, Helsinki, Finland Finnish Inst Occupat Hlth Helsinki Finland & Toxicol, Helsinki, Finland
Titolo Testata:
FEBS LETTERS
fascicolo: 1, volume: 448, anno: 1999,
pagine: 105 - 110
SICI:
0014-5793(19990401)448:1<105:CAPDOA>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN LIVER-MICROSOMES; CYTOCHROME-P450 2A6 CYP2A6; COUMARIN 7-HYDROXYLATION; INTERINDIVIDUAL VARIABILITY; C-OXIDATION; NICOTINE; METABOLISM; POLYMORPHISM; CLUSTER; DEBRISOQUINE;
Keywords:
cytochrome P450; coumarin; gene deletion; unequal crossover; genotype; phenotype;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Ingelman-Sundberg, M KarolinskaStockholm,l Inst Environm Med, Div Mol Toxicol, Box 210, S-17177 Karolinska Inst Box 210 Stockholm Sweden S-17177 177
Citazione:
M. Oscarson et al., "Characterisation and PCR-based detection of a CYP2A6 gene deletion found at a high frequency in a Chinese population", FEBS LETTER, 448(1), 1999, pp. 105-110

Abstract

Cytochrome P450 2A6 is an important human hepatic P450 which activates pre-carcinogens, oxidises some drugs and constitutes the major nicotine C-oxidase, In fact, results have been presented in the literature which suggesteda relationship between the distribution of defective CYP2A6 alleles and smoking behaviour as well as cigarette consumption. In the present report, wedescribe the structure of a novel CYP2A locus where the whole CYP2A6 gene has been deleted, resulting in an abolished cytochrome P450 2A6-dependent metabolism. The origin of this locus is apparently due to an unequal crossover event between the 3'-flanking region of the CYP2A6 and CYP2A7 genes, A rapid PCR-based method for the detection of the CYP2A6del allele was developed and the allele frequency was 15.1% among 96 Chinese subjects, but only 1.0% in Finns (n=100) and 0.5% in Spaniards (n=100), In the Chinese population, we did not detect any CYP2A6*2 alleles using an improved genotyping procedure, in contrast to the 11-20% previously reported. It is concluded thatgenotyping for the CYP2A6del allele is of great importance in studies correlating, for example, smoking behaviour, pre-carcinogen activation or drug metabolism to the CYP2A6 genotype, in particular when oriental populations are investigated. (C) 1999 Federation of European Biochemical Societies.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 12/07/20 alle ore 06:43:45