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Titolo:
Decreased capacity for debrisoquine metabolism among black Tanzanians: analyses of the CYP2D6 genotype and phenotype
Autore:
Wennerholm, A; Johansson, I; Massele, AY; Jande, M; Alm, C; Aden-Abdi, Y; Dahl, ML; Ingelman-Sundberg, M; Bertilsson, L; Gustafsson, LL;
Indirizzi:
Huddinge Univ Hosp, Karolinska Inst, Dept Med Lab Sci & Technol, Div Clin Pharmacol, S-14186 Huddinge, Sweden Huddinge Univ Hosp Huddinge Sweden S-14186 col, S-14186 Huddinge, Sweden Karolinska Inst, Inst Environm Med, Div Mol Toxicol, S-10401 Stockholm, Sweden Karolinska Inst Stockholm Sweden S-10401 icol, S-10401 Stockholm, Sweden Muhimbili Med Ctr, Dept Clin Pharmacol, Dar Es Salaam, Tanzania Muhimbili Med Ctr Dar Es Salaam Tanzania macol, Dar Es Salaam, Tanzania
Titolo Testata:
PHARMACOGENETICS
fascicolo: 6, volume: 9, anno: 1999,
pagine: 707 - 714
SICI:
0960-314X(199912)9:6<707:DCFDMA>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
MEPHENYTOIN HYDROXYLATION PHENOTYPES; S-MEPHENYTOIN; SWEDISH POPULATION; CYTOCHROME-P450 CYP2D6; ZIMBABWEAN POPULATION; GENETIC-POLYMORPHISM; MOLECULAR-BASIS; CHINESE; SPARTEINE; ALLELES;
Keywords:
CYP2D locus; genetic polymorphism; Bantu; extensive metabolizers;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Wennerholm, A Huddinge Univ Hosp, Karolinska Inst, Dept Med Lab Sci & Technol, Div Clin Pharmacol, S-14186 Huddinge, Sweden Huddinge Univ Hosp Huddinge Sweden S-14186 uddinge, Sweden
Citazione:
A. Wennerholm et al., "Decreased capacity for debrisoquine metabolism among black Tanzanians: analyses of the CYP2D6 genotype and phenotype", PHARMACOGEN, 9(6), 1999, pp. 707-714

Abstract

The cytochrome P450 2D6 (CYP2D6) genotypes and phenotypes of 106 unrelated, healthy black: Tanzanians of Bantu origin were investigated. The results revealed a population with a generally decreased capacity to metabolize theCYP2D6 substrate debrisoquine with 59% of the Tanzanian extensive metabolisers having debrisoquine metabolic ratios (MRs) > 1 versus 20% in Caucasians, This decrease in metabolic capacity was not fully explained by the partially or fully detrimental CYP2D6 gene mutations analysed for in this study. As many as 7% poor metabolizers of debrisoquine were identified but none was homozygous for defective CYP2D6 alleles, The majority among the group ofpoor metabolizers had relatively low metabolic ratios. The mutational profile indicated a closer association of the Tanzanian CYP2D locus to that of Zimbabweans rather than to that of Ethiopians, The defective alleles CYP2D6*3, *4, *5 and *6 were found at low frequencies (0%, 1%, 6%, 0%, respectively), whereas the CYP2D6*17 allele causing an enzyme with altered specificity was common (allele frequency = 17%), It is concluded that the CYP2D6 genotype in the Tanzanian Bantu population is different from that of other African populations examined to date and that further studies are required to explain the generally lower capacity to metabolize CYP2D6 substrates, Pharmacogenetics 9:707-714 (C) 1999 Lippincott Williams & Wilkins.

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Documento generato il 25/01/20 alle ore 06:29:28