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Titolo:
Allele and genotype frequencies of polymorphic cytochromes P4502D6, 2C19 and 2E1 in Aborigines from Western Australia
Autore:
Griese, EU; Ilett, KF; Kitteringham, NR; Eichelbaum, M; Powell, H; Spargo, RM; LeSouef, PN; Musk, AW; Minchin, RF;
Indirizzi:
Univ Western Australia, Dept Pharmacol, Nedlands, WA 6907, Australia Univ Western Australia Nedlands WA Australia 6907 nds, WA 6907, Australia Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany Dr Margarete Fischer Bosch Inst Clin Pharmacol Stuttgart Germany ermany Western Australian Ctr Pathol & Med Res, Clin Pharmacol & Toxicol Lab, Nedlands, WA, Australia Western Australian Ctr Pathol & Med Res Nedlands WA Australia Australia Univ Liverpool, Dept Pharmacol & Therapeut, Liverpool L69 3BX, Merseyside,England Univ Liverpool Liverpool Merseyside England L69 3BX X, Merseyside,England Univ Western Australia, Dept Paediat, Nedlands, WA 6009, Australia Univ Western Australia Nedlands WA Australia 6009 nds, WA 6009, Australia Sir Charles Gairdner Hosp, Dept Resp Med, Nedlands, WA 6009, Australia SirCharles Gairdner Hosp Nedlands WA Australia 6009 , WA 6009, Australia Royal Perth Hosp, Lab Canc Med, Perth, WA, Australia Royal Perth Hosp Perth WA Australia , Lab Canc Med, Perth, WA, Australia
Titolo Testata:
PHARMACOGENETICS
fascicolo: 1, volume: 11, anno: 2001,
pagine: 69 - 76
SICI:
0960-314X(200102)11:1<69:AAGFOP>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
FRAGMENT-LENGTH-POLYMORPHISM; DRUG-METABOLIZING-ENZYMES; POLYMERASE-CHAIN-REACTION; HUMAN CYP2E1 GENE; S-MEPHENYTOIN; LUNG-CANCER; AFRICAN POPULATION; 5'-FLANKING REGION; CYP2C19; DEBRISOQUINE;
Keywords:
CYP2D6; CYP2C19; CYP2E1; genetic polymorphism; Australian aborigine;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
54
Recensione:
Indirizzi per estratti:
Indirizzo: Ilett, KF Univ Western Australia, Dept Pharmacol, Nedlands, WA 6907, Australia Univ Western Australia Nedlands WA Australia 6907 07, Australia
Citazione:
E.U. Griese et al., "Allele and genotype frequencies of polymorphic cytochromes P4502D6, 2C19 and 2E1 in Aborigines from Western Australia", PHARMACOGEN, 11(1), 2001, pp. 69-76

Abstract

The polymorphisms of the important xenobiotic metabolizing enzymes CYP2D6,CYP2C19 and CYP2E1 have been studied extensively in a large number of populations and show significant heterogeneity in the frequency of different alleles/genotypes and in the prevalence of the extensive and poor metabolizerphenotypes, Understanding of inter-ethnic differences in genotypes is important in prediction of either beneficial or adverse effects from therapeutic agents and other xenobiotics. Since no data were available for AustralianAborigines, we investigated the frequencies of alleles and genotypes for CYP2D6, CYP2C19 and CYP2E1 in a population living in the far north of Western Australia. Because of its geographical isolation, this population can serve as a model to study the impact of evolutionary forces on the distribution of different alleles for xenobiotic metabolizing enzymes. Twelve CYP2D6 alleles were analysed, The wild-type allele *1 was the most frequent (85.8%)and the non-functional alleles (*4, *5, *16) had an overall frequency of less than 10%. Only one subject (0.4%) was a poor metabolizer for CYP2D6 because of the genotype *5/*5, For CYP2C19, the frequencies of the *1 (wild-type) and the non-functional (*2 and *3) alleles were 50.2%, 35.5% and 14.3%,respectively. The combined CYP2C19 genotypes (*2/*2, *2/*3 or *3/*3) correspond to a predicted frequency of 25.6% for the CYP2C19 poor metabolizer phenotype, For CYP2E1, only one subject had the rare c2 allele giving an overall allele frequency of 0.2%. For CYP2D6 and CYP2C19, allele frequencies and predicted phenotypes differed significantly from those for Caucasians butwere similar to those for Orientals indicating a close relationship to East Asian populations. Differences between Aborigines and Orientals in allelefrequencies for CYP2D6*10 and CYP2E1 c2 may have arisen through natural selection, or genetic drift, respectively, Pharmacogenetics 11:69-76 (C) 2001Lippincott Williams & Wilkins.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 15:33:31