Genetic polymorphisms in glutathione S-transferase M1 and T1 in an Australian Aborigine population

Ilett, K. F.; McCormick, Nora; Carpenter, DS; Spargo, R.M.; Souëf, P. Le; Musk, A.W.; Minchin, Rodney F.

doi:10.1097/00008571-200007000-00011

Cited by 2 publications

(4 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The frequency of the low activity CYP2D6*10 (0.8%) and CYP2D6*17 (0.2%) alleles contrasts with the 51% and 34% frequencies observed in Asians and Africans respectively (Table 2). Significantly, the proportion of all loss of function and impairment mutations of CYP2D6 was low in these Aborigines, while the proportion of the functional CYP2D6*1 allele (85%) was the highest observed in any racial group 83 . This is perhaps consistent with the Australoid ancestry of Aborigines or specific adaption to the unique metabolic challenges of Australian native foods.…”

Section: Inter-ethnic Variation In Cyp2d6mentioning

confidence: 81%

“…This is perhaps consistent with the Australoid ancestry of Aborigines or specific adaption to the unique metabolic challenges of Australian native foods. Further studies are necessary to determine if ethnically pure Aborigines throughout the Australian continent share the robust EM profile demonstrated in this initial study 83 .…”

Section: Inter-ethnic Variation In Cyp2d6mentioning

confidence: 93%

“…These include 10% of Northern Spanish 74 Data was modified from Ingelmann-Sundberg et al 9 . Also included are some very recent CYP2D6 genotyping data from an isolated and ethnically pure Aboriginal community (n=239) 83 . 2D6*5 and *16 are deletion mutations, these occur at a similar frequency in all the populations, and probably occurred before the evolutionary separation of Caucasians, Negroids and Mongoloids, over 150,000 years ago 70,83,102 .…”

Section: Inter-ethnic Variation In Cyp2d6mentioning

confidence: 99%

“…Also included are some very recent CYP2D6 genotyping data from an isolated and ethnically pure Aboriginal community (n=239) 83 . 2D6*5 and *16 are deletion mutations, these occur at a similar frequency in all the populations, and probably occurred before the evolutionary separation of Caucasians, Negroids and Mongoloids, over 150,000 years ago 70,83,102 . The latest updates of allelic and functional variations for all the cytochrome P450 enzymes can be found at the webpage: http://www.imm.ki.se/CYPalleles/ dosage of primary drugs otherwise rapidly inactivated by CYP2D6 78 .…”

Section: Inter-ethnic Variation In Cyp2d6mentioning

confidence: 99%

See 3 more Smart Citations

Variable Cytochrome P450 2D6 Expression and Metabolism of Codeine and Other Opioid Prodrugs: Implications for the Australian Anaesthetist

Wilcox

Owen

2000

Anaesth Intensive Care

View full text Add to dashboard Cite

Codeine is a popular opioid prodrug dependent on the activity of the specific cytochrome P450 enzyme 2D6 (CYP2D6). This enzyme catalyses the production of the potent analgesic metabolite morphine, but genetic studies have demonstrated that individuals from different ethnic groups exhibit considerable variability in the functional capacities of their expressed CYP2D6 enzymes, and pharmacological studies have shown many commonly prescribed drugs can reduce the action of CYP2D6 enzymes. These findings have significant clinical implications for the rational prescription of effective analgesia, especially in a multicultural country like Australia.

show abstract

Section: Inter-ethnic Variation In Cyp2d6mentioning

confidence: 81%

Section: Inter-ethnic Variation In Cyp2d6mentioning

confidence: 93%

Section: Inter-ethnic Variation In Cyp2d6mentioning

confidence: 99%

Section: Inter-ethnic Variation In Cyp2d6mentioning

confidence: 99%

See 2 more Smart Citations

Variable Cytochrome P450 2D6 Expression and Metabolism of Codeine and Other Opioid Prodrugs: Implications for the Australian Anaesthetist

Wilcox

Owen

2000

Anaesth Intensive Care

View full text Add to dashboard Cite

show abstract

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

et al. 2001

View full text Add to dashboard Cite

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 (85.81%) 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 CYP2EI, 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.

show abstract

Genetic polymorphisms in glutathione S-transferase M1 and T1 in an Australian Aborigine population

Cited by 2 publications

References 25 publications

Variable Cytochrome P450 2D6 Expression and Metabolism of Codeine and Other Opioid Prodrugs: Implications for the Australian Anaesthetist

Variable Cytochrome P450 2D6 Expression and Metabolism of Codeine and Other Opioid Prodrugs: Implications for the Australian Anaesthetist

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

Contact Info

Product

Resources

About