Interethnic diversity of NAT2 polymorphisms in Brazilian admixed populations

Overall, there were no statistically significant differences in the distribution of NAT2 polymorphism when Afro-Brazilian and White groups were compared. Even the allele frequency of 191A, relatively common in African descendents, was not different between the Afro-Brazilian and White groups. However, allele and genotype frequencies of G590A were significantly higher in the Amerindian group than either in the Afro-Brazilian or White groups. Interestingly, a haplotype block between G590A and A803G was verified exclusively among Amerindians.Our results indicate that ethnic admixture might contribute to a particular pattern of genetic diversity in the NAT2 gene and also offer new insights for the investigation of possible new NAT2 gene-environment effects in admixed populations.Genetic functional polymorphisms of xenobiotic/drug metabolizing enzymes have been associated with pharmacotherapy response differences and disease risk susceptibility [1,2]. Special emphasis has been placed on a phase II metabolizing enzyme, N-acetyltransferase type 2 (Nat2, EC 2.3.1.5), a milestone in the pharmacogenetics field as one of the first enzymes to be associated as a cause of interindividual variation in drug metabolism [3]. Nat2 catalyzes a transfer of an acetyl group from the cofactor acetyl-coenzyme A (acetyl-CoA) to the amine nitrogen atom of aromatic amines and hydrazines [4]. This enzyme is important in the aromatic and heterocyclic amine conjugating reaction, preventing their metabolic activation into electrophilic intermediates that could initiate DNA damage and potentially induce carcinogenic mutations [5]. Moreover, Nat2 plays a role in the metabolism of different hydrazine and arylamine drugs, such as isoniazid and dapsone, both used in the treatment of Mycobacterium spp. infections [6,7].The human NAT2 gene has an intronless open reading frame of 870 base pairs and is primarily expressed in the liver and intestines [8-10]. It has long been recognized that some single nucl