Universidade Estadual de Santa Cruz, Laboratório de Farmacogenômica e Epidemiologia Molecular (LAFEM), Ilhéus, Bahia, Brazil.
BMC Genet. 2010 Oct 5;11:87. doi: 10.1186/1471-2156-11-87.
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 NAT2 gene remain a focus for the potential discoveries in personalized drug therapy and genetic markers of diseases. Despite the wide characterization of NAT2 SNPs frequency in established ethnic groups, little data are available for highly admixed populations. In this context, five common NAT2 SNPs (G191A, C481T, G590A, A803G and G857A) 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 NAT2 polymorphism is different among these three ethnic groups.
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.
N-乙酰基转移酶 2 型（Nat2）是一种 II 相药物代谢酶，在芳香族和杂环胺的生物活化中起着关键作用。其在药物代谢和疾病易感性中的相关性仍然是药物遗传学研究的一个核心主题，主要是因为其在人类群体中的遗传变异性。事实上，NAT2 基因上的进化和特定种族的单核苷酸多态性仍然是个性化药物治疗和疾病遗传标志物的潜在发现的焦点。尽管已经广泛描述了在已建立的种族群体中 NAT2SNP 的频率，但对于高度混合的人群，可用的数据很少。在这种情况下，对巴西东北部的非裔巴西人、白人和美洲印第安人组成的高度混合人群进行了五个常见的 NAT2SNP（G191A、C481T、G590A、A803G 和 G857A）的研究。因此，我们试图确定 NAT2 多态性的分布在这三个种族群体中是否不同。
总体而言，当比较非裔巴西人和白人时，NAT2 多态性的分布没有统计学上的显著差异。即使相对常见于非洲后裔的 191A 等位基因频率在非裔巴西人和白人之间也没有差异。然而，G590A 的等位基因和基因型频率在美洲印第安人组中明显高于非裔巴西人或白人组。有趣的是，仅在美洲印第安人中发现了 G590A 和 A803G 之间的单倍型块。
我们的结果表明，种族混合可能导致 NAT2 基因中特定的遗传多样性模式，并为混合人群中可能存在的新 NAT2 基因-环境相互作用的研究提供新的见解。
