Allele and genotype frequencies of polymorphic cytochromes P4502D6, 2C19 and 2E1 in Aborigines from Western Australia

被引:48
作者
Griese, EU
Ilett, KF [1 ]
Kitteringham, NR
Eichelbaum, M
Powell, H
Spargo, RM
LeSouef, PN
Musk, AW
Minchin, RF
机构
[1] Univ Western Australia, Dept Pharmacol, Nedlands, WA 6907, Australia
[2] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany
[3] Western Australian Ctr Pathol & Med Res, Clin Pharmacol & Toxicol Lab, Nedlands, WA, Australia
[4] Univ Liverpool, Dept Pharmacol & Therapeut, Liverpool L69 3BX, Merseyside, England
[5] Univ Western Australia, Dept Paediat, Nedlands, WA 6009, Australia
[6] Sir Charles Gairdner Hosp, Dept Resp Med, Nedlands, WA 6009, Australia
[7] Royal Perth Hosp, Lab Canc Med, Perth, WA, Australia
来源
PHARMACOGENETICS | 2001年 / 11卷 / 01期
关键词
CYP2D6; CYP2C19; CYP2E1; genetic polymorphism; Australian aborigine;
D O I
10.1097/00008571-200102000-00008
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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 metabolizer phenotypes, 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 Australian Aborigines, 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 but were similar to those for Orientals indicating a close relationship to East Asian populations. Differences between Aborigines and Orientals in allele frequencies for CYP2D6*10 and CYP2E1 c2 may have arisen through natural selection, or genetic drift, respectively, Pharmacogenetics 11:69-76 (C) 2001 Lippincott Williams & Wilkins.
引用
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页码:69 / 76
页数:8
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