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Titolo:
Structural characterization of a new variant of the CYP2A6 gene (CYP2A6*1B) apparently diagnosed as heterozygotes of CYP2A6*1A and CYP2A6*4C
Autore:
Ariyoshi, N; Takahashi, Y; Miyamoto, M; Umetsu, Y; Daigo, S; Tateishi, T; Kobayashi, S; Mizorogi, Y; Loriot, MA; Stucker, I; Beaune, P; Kinoshita, M; Kamataki, T;
Indirizzi:
Hokkaido Univ, Grad Sch Pharmaceut Sci, Lab Drug Metab, Div Pharmacobiodynam,Kita Ku, Sapporo, Hokkaido 0600812, Japan Hokkaido Univ Sapporo Hokkaido Japan 0600812 oro, Hokkaido 0600812, Japan St Marianna Univ, Sch Med, Dept Pharmacol, Kanagawa, Japan St Marianna Univ Kanagawa Japan ch Med, Dept Pharmacol, Kanagawa, Japan To Kokai Daiichi Hosp, Clin Pharmacol Ctr, Tokyo, Japan To Kokai Daiichi Hosp Tokyo Japan osp, Clin Pharmacol Ctr, Tokyo, Japan Univ Paris 05, INSERM, U490, Paris, France Univ Paris 05 Paris FranceUniv Paris 05, INSERM, U490, Paris, France Otsuka Pharmaceut Co Ltd, Tokushima 77101, Japan Otsuka Pharmaceut Co LtdTokushima Japan 77101 d, Tokushima 77101, Japan
Titolo Testata:
PHARMACOGENETICS
fascicolo: 8, volume: 10, anno: 2000,
pagine: 687 - 693
SICI:
0960-314X(200011)10:8<687:SCOANV>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN LIVER-MICROSOMES; COUMARIN 7-HYDROXYLATION; INTERINDIVIDUAL VARIABILITY; CYTOCHROME-P450 2A6; DELETION; IDENTIFICATION; METABOLISM; NICOTINE; ACID; HYDROCHLORIDE;
Keywords:
cytochrome P450; genetic polymorphism; genotyping; 3 '-untranslated region;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
25
Recensione:
Indirizzi per estratti:
Indirizzo: Kamataki, T Hokkaido Univ, Grad Sch Pharmaceut Sci, Lab Drug Metab, Div Pharmacobiodynam,Kita Ku, N12W6, Sapporo, Hokkaido 0600812, Japan Hokkaido Univ N12W6 Sapporo Hokkaido Japan 0600812 0812, Japan
Citazione:
N. Ariyoshi et al., "Structural characterization of a new variant of the CYP2A6 gene (CYP2A6*1B) apparently diagnosed as heterozygotes of CYP2A6*1A and CYP2A6*4C", PHARMACOGEN, 10(8), 2000, pp. 687-693

Abstract

During the course of investigating the frequency of a CYP2A6 whole deletion-type polymorphism (CYP2A6*4C) in Japanese, an unexpectedly large population of heterozygotes for CYP2A6*4C and the wild-type (CYP2A6*1A) was found. Cloning of a cDNA encoding CYP2A6 from the liver of individuals judged as heterozygotes for CYP2A6*4C and the CYP2A6*1A was carried out to identify the causal allele(s) responsible for a possible overestimation. A clone isolated from the liver cDNA library possessed 58 bp sequences in the 3'-untranslated region, which was replaced with the corresponding region of the CYP2A7 gene. The same gene conversion existed in the genomic DNA, indicating that the replacement was not a cloning artifact. Based on the gene structure of the allele (CYP2A6*1B), this variant was thought to be one of the causal alleles responsible for overestimation of heterozygotes for CYP2A6*4C and CYP2A6*1A. To investigate this further, we developed a genotyping method which could distinguish the CYP2A6*1A, CYP2A6*1B and CYP2A6*4C alleles from each other. The results clearly showed that CYP2A6*1B was the sole allele responsible for the overestimation. We conclude that the new genotyping methodallows determination of six genotypes of the CYP2A6 gene, simultaneously and precisely, in both Oriental and Caucasian populations. Pharmacogenetics 10:687-693 (C) 2000 Lippincott Williams & Wilkins.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 21:03:40