Abstract
N-acetyltransferase 2 (NAT2) is responsible for metabolizing xenobiotics; NAT2 polymorphisms lead to three phenotypes: rapid, intermediate and slow acetylators. We aimed to investigate NAT2 diversity in Native Americans. NAT2 exon 2 was sequenced for 286 individuals from 21 populations (Native American and American Mestizos). Excluding the basal/rapid haplotype NAT2*4, the most frequent haplotypes are NAT2*5B (35.95%) in hunter-gatherers and NAT2*7B (20.61%) and NAT2*5B (19.08%) in agriculturalists that were related to the slow phenotype. A new haplotype was identified in two Amerindians. Data from the ~44 kb region surrounding NAT2 in 819 individuals from Africa, East-Asia, Europe and America were used in additional analyses. No significant differences in the acetylator NAT2 haplotype and phenotype distributions were found between Native American populations practicing farming and/or herding and those practicing hunting and gathering, probably because of the absence or weakness of selection pressures and presence of demographic and random processes preventing detection of any selection signal.
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Acknowledgements
We are grateful to the individuals who donated the samples analyzed here and to the Fundação Nacional do Índio (FUNAI) for logistic support in the Brazilian sample collections. We thank Sandro L Bonatto for donating the Siberian Eskimo samples. We are also grateful to Michele Aramburu Serafini for technical assistance, Luciana Tovo-Rodrigues for information about the software used and Sidia M Callegari-Jacques and Diego Rovaris for help with the statistical analysis. Financial support was provided by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Programa de Apoio a Núcleos de Excelência (FAPERGS/PRONEX). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
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Bisso-Machado, R., Ramallo, V., Paixão-Côrtes, V. et al. NAT2 gene diversity and its evolutionary trajectory in the Americas. Pharmacogenomics J 16, 559–565 (2016). https://doi.org/10.1038/tpj.2015.72
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DOI: https://doi.org/10.1038/tpj.2015.72
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