ACETYLATION PHENOTYPE AND GENOTYPE IN ABORIGINAL LEPROSY PATIENTS FROM THE NORTH-WEST REGION OF WESTERN-AUSTRALIA

N-Acetyltransferases (NAT1, NAT2) play an important role in biotransfo rmation of a number of drugs and carcinogens. A polymorphism in the me tabolism of such compounds by NAT2 has been known for many years but i t is only recently that the underlying molecular genetics has been elu cidated. In the present study, we have correlated acetylation phenotyp e 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 Austral ia. 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 o f 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 pr oportion of M3 mutations reported for any ethnic population. The obser ved genotype proportions were not significantly different from those p redicted by the Hardy-Weinberg Law (chi2 = 1.07, p > 0.05). Phenotype was predictable from genotype in 100% of patients. At the time of stud y, 29 of the Aborigines were receiving acedapsone intramuscularly for control of leprosy. Plasma dapsone concentrations in these patients we re similar for both slow (n = 11) and rapid (n = 18) acetylators, sugg esting that phenotype is unlikely to influence treatment outcome. The data show that Aborigines have a similar phenotype distribution to tha t of some Asian populations, but that there are differences in the fre quencies of the M1, M2 and M3 mutant alleles. We suggest that acetylat ion genotyping may be a useful tool for investigation of the anthropol ogical links between population groups around the Asia-Pacific rim.