Acetylation phenotype and genotype in Aboriginal leprosy patients from the north-west region of Western Australia

Kenneth Ilett, G.M. Chiswell, R.M. Spargo, E. Platt, R.F. Minchin

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Abstract

N-Acetyltransferases (NAT1, NAT2) play an important role in biotransformation of a number of drugs and carcinogens. A polymorphism in the metabolism of such compounds by NAT2 has been known for many years but it is only recently that the underlying molecular genetics has been elucidated. In the present study, we have correlated acetylation phenotype and genotype in a group of 49 Australian Aborigines (26 males and 23 females; mean age = 50.5 yr) from the Derby region of Western Australia. Phenotype was determined using caffeine and genotype by an allele-specific polymerase chain reaction. The percentages of slow and rapid phenotypes were 36.7 and 63.3%, respectively, while the distribution of alleles for the NAT2 gene was 41% for the wildtype and 2, 17 and 40% for the M1, M2 and M3 mutations, respectively. This is the highest proportion of M3 mutations reported for any ethnic population. The observed genotype proportions were not significantly different from those predicted by the Hardy-Weinberg Law (chi2 = 1.07, p > 0.05). Phenotype was predictable from genotype in 100% of patients. At the time of study, 29 of the Aborigines were receiving acedapsone intramuscularly for control of leprosy. Plasma dapsone concentrations in these patients were similar for both slow (n = 11) and rapid (n = 18) acetylators, suggesting that phenotype is unlikely to influence treatment outcome. The data show that Aborigines have a similar phenotype distribution to that of some Asian populations, but that there are differences in the frequencies of the M1, M2 and M3 mutant alleles. We suggest that acetylation genotyping may be a useful tool for investigation of the anthropological links between population groups around the Asia-Pacific rim.
Original languageEnglish
Pages (from-to)264-269
JournalPharmacogenetics
Volume3
DOIs
Publication statusPublished - 1993

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Western Australia
Leprosy
Acetylation
Genotype
Phenotype
Alleles
Acedapsone
Oceanic Ancestry Group
Dapsone
Mutation
Acetyltransferases
Time and Motion Studies
Anthropology
Biotransformation
Caffeine
Population Groups
Carcinogens
Population
Molecular Biology
Polymerase Chain Reaction

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Ilett, Kenneth ; Chiswell, G.M. ; Spargo, R.M. ; Platt, E. ; Minchin, R.F. / Acetylation phenotype and genotype in Aboriginal leprosy patients from the north-west region of Western Australia. In: Pharmacogenetics. 1993 ; Vol. 3. pp. 264-269.
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abstract = "N-Acetyltransferases (NAT1, NAT2) play an important role in biotransformation of a number of drugs and carcinogens. A polymorphism in the metabolism of such compounds by NAT2 has been known for many years but it is only recently that the underlying molecular genetics has been elucidated. In the present study, we have correlated acetylation phenotype and genotype in a group of 49 Australian Aborigines (26 males and 23 females; mean age = 50.5 yr) from the Derby region of Western Australia. Phenotype was determined using caffeine and genotype by an allele-specific polymerase chain reaction. The percentages of slow and rapid phenotypes were 36.7 and 63.3{\%}, respectively, while the distribution of alleles for the NAT2 gene was 41{\%} for the wildtype and 2, 17 and 40{\%} for the M1, M2 and M3 mutations, respectively. This is the highest proportion of M3 mutations reported for any ethnic population. The observed genotype proportions were not significantly different from those predicted by the Hardy-Weinberg Law (chi2 = 1.07, p > 0.05). Phenotype was predictable from genotype in 100{\%} of patients. At the time of study, 29 of the Aborigines were receiving acedapsone intramuscularly for control of leprosy. Plasma dapsone concentrations in these patients were similar for both slow (n = 11) and rapid (n = 18) acetylators, suggesting that phenotype is unlikely to influence treatment outcome. The data show that Aborigines have a similar phenotype distribution to that of some Asian populations, but that there are differences in the frequencies of the M1, M2 and M3 mutant alleles. We suggest that acetylation genotyping may be a useful tool for investigation of the anthropological links between population groups around the Asia-Pacific rim.",
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Acetylation phenotype and genotype in Aboriginal leprosy patients from the north-west region of Western Australia. / Ilett, Kenneth; Chiswell, G.M.; Spargo, R.M.; Platt, E.; Minchin, R.F.

In: Pharmacogenetics, Vol. 3, 1993, p. 264-269.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Acetylation phenotype and genotype in Aboriginal leprosy patients from the north-west region of Western Australia

AU - Ilett, Kenneth

AU - Chiswell, G.M.

AU - Spargo, R.M.

AU - Platt, E.

AU - Minchin, R.F.

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AB - N-Acetyltransferases (NAT1, NAT2) play an important role in biotransformation of a number of drugs and carcinogens. A polymorphism in the metabolism of such compounds by NAT2 has been known for many years but it is only recently that the underlying molecular genetics has been elucidated. In the present study, we have correlated acetylation phenotype and genotype in a group of 49 Australian Aborigines (26 males and 23 females; mean age = 50.5 yr) from the Derby region of Western Australia. Phenotype was determined using caffeine and genotype by an allele-specific polymerase chain reaction. The percentages of slow and rapid phenotypes were 36.7 and 63.3%, respectively, while the distribution of alleles for the NAT2 gene was 41% for the wildtype and 2, 17 and 40% for the M1, M2 and M3 mutations, respectively. This is the highest proportion of M3 mutations reported for any ethnic population. The observed genotype proportions were not significantly different from those predicted by the Hardy-Weinberg Law (chi2 = 1.07, p > 0.05). Phenotype was predictable from genotype in 100% of patients. At the time of study, 29 of the Aborigines were receiving acedapsone intramuscularly for control of leprosy. Plasma dapsone concentrations in these patients were similar for both slow (n = 11) and rapid (n = 18) acetylators, suggesting that phenotype is unlikely to influence treatment outcome. The data show that Aborigines have a similar phenotype distribution to that of some Asian populations, but that there are differences in the frequencies of the M1, M2 and M3 mutant alleles. We suggest that acetylation genotyping may be a useful tool for investigation of the anthropological links between population groups around the Asia-Pacific rim.

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JO - Pharmacogenetics

JF - Pharmacogenetics

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