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Titolo:
Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver
Autore:
Lang, T; Klein, K; Fischer, J; Nussler, AK; Neuhaus, P; Hofmann, U; Eichelbaum, M; Schwab, M; Zanger, UM;
Indirizzi:
Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, GermanyDr Margarete Fischer Bosch Inst Clin Pharmacol Stuttgart Germany D-70376 Humboldt Univ, Campus Virchow Clin, Dept Surg, Berlin, Germany Humboldt Univ Berlin Germany s Virchow Clin, Dept Surg, Berlin, Germany
Titolo Testata:
PHARMACOGENETICS
fascicolo: 5, volume: 11, anno: 2001,
pagine: 399 - 415
SICI:
0960-314X(200107)11:5<399:EGPITH>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYTOCHROME P450IIB6 GENE; N-DEMETHYLATION; RECEPTOR CAR; CATALYTIC ACTIVITY; METABOLISM; MICROSOMES; BUPROPION; INDUCTION; FORMS; IDENTIFICATION;
Keywords:
CYP2B6; genetic polymorphism; pharmacogenetics;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Fischer, J Dr Margarete Fischer Bosch Inst Clin Pharmacol, Auerbachstr 112, D-70376 Stuttgart, Germany Dr Margarete Fischer Bosch Inst Clin PharmacolAuerbachstr 112 Stuttgart Germany D-70376
Citazione:
T. Lang et al., "Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver", PHARMACOGEN, 11(5), 2001, pp. 399-415

Abstract

The human cytochrome P450, CYP2B6, is involved in the metabolism of several therapeutically important drugs and environmental or abused toxicants, Inthis study, we present the first systematic Investigation of genetic polymorphism in the CYP2B6 gene on chromosome 19, A specific direct: sequencing strategy was developed based on CYP2B6 and CYP2B7 genomic sequence information and DNA from 35 subjects was completely analysed for mutations throughout all nine exons and their exon-intron boundaries, A total of nine novel point mutations were identified, of which five result in amino acid substitutions in exon 1 (664T, Arg(22)Cys), exon 4 (G516T, Gln(172)His), exon 5 (C777A, Ser(259)Arg and A785G, Lys(262)Arg) and exon 9 (C1459T, Arg(487)Cys) and four are silent mutations (C78T, G216C, G714A and C732T), Polymerase chain reaction-restriction fragment length polymorphism tests were developed to detect each of the five nonsynonymous mutations in genomic DNA, By screening a population of 215 subjects the C64T, G516T, C777A, A785G and C1459T mutations were found at frequencies of 5.3%, 28.6%, 0.5%, 32.6% and 14.0%, respectively, Haplotype analysis revealed six different mutant alleles termed CYP2B6*2 (C64T), *3 (C777A), *4 (A785G), *5 (C1459T), *6 (G516T and A785G) and *7 (G516T, A785G and C1459T). By analysing a large number of human liver samples, significantly reduced CYP2B6 protein expression and S-mephenytoin N-demethylase activity were found in carriers of the C1459T (R487C) mutation (alleles *5 and *7), These data demonstrate that the extensive interindividual variability of CYP2B6 expression and function is not only due to regulatory phenomena, but also caused by a common genetic polymorphism, Pharmacogenetics 11:399-415 (C) 2001 Lippincott Williams & Wilkins.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 19:54:57