Interethnic diversity of NAT2 polymorphisms in Brazilian admixed populations

<p>Abstract</p> <p>Background</p> <p>N-acetyltransferase type 2 (Nat2) is a phase II drug- metabolizing enzyme that plays a key role in the bioactivation of aromatic and heterocyclic amines. Its relevance in drug metabolism and disease susceptibility remains a central theme for pharmacogenetic research, mainly because of its genetic variability among human populations. In fact, the evolutionary and ethnic-specific SNPs on the <it>NAT2 </it>gene remain a focus for the potential discoveries in personalized drug therapy and genetic markers of diseases. Despite the wide characterization of <it>NAT2 </it>SNPs frequency in established ethnic groups, little data are available for highly admixed populations. In this context, five common <it>NAT2 </it>SNPs (<it>G191A</it>, <it>C481T</it>, <it>G590A</it>, <it>A803G </it>and G<it>857A</it>) were investigated in a highly admixed population comprised of Afro-Brazilians, Whites, and Amerindians in northeastern Brazil. Thus, we sought to determine whether the distribution of <it>NAT2 </it>polymorphism is different among these three ethnic groups.</p> <p>Results</p> <p>Overall, there were no statistically significant differences in the distribution of <it>NAT2 </it>polymorphism when Afro-Brazilian and White groups were compared. Even the allele frequency of <it>191A</it>, relatively common in African descendents, was not different between the Afro-Brazilian and White groups. However, allele and genotype frequencies of <it>G590A </it>were significantly higher in the Amerindian group than either in the Afro-Brazilian or White groups. Interestingly, a haplotype block between <it>G590A </it>and <it>A803G </it>was verified exclusively among Amerindians.</p> <p>Conclusions</p> <p>Our results indicate that ethnic admixture might contribute to a particular pattern of genetic diversity in the <it>NAT2 </it>gene and also offer new insights for the investigation of possible new <it>NAT2 </it>gene-environment effects in admixed populations.</p