NAT2 PHENOTYPIC DIVERSITY IN NATIVE POPULATIONS

BISSO-MACHADO, R; RAMALLO, V; PAIXÃO-CÔRTES, VR; SALZANO, FM; HÜNEMEIER, T; BORTOLINI, MC

Congreso; 59 Congresso Brasileiro de Genética; 2013

NAT2 (N-acetyltransferase 2) is responsible for the metabolism of xenobiotics. It is also responsible for the metabolization of several chemicals present in the diet, like the ones found in overcooked meat. e polymorphisms found in NAT2 give origin to two functional phenotypes: rapid and slow acetylators. Rapid acetylators are generally more e ective in metabolizing xenobiotics, the inverse occurring with the slow ones. Di erences in diet can be correlated with variation in metabolic phenotype frequencies, and it is well known that Native Americans have a rich and variable diet, with the presence of many xenobiotics. e present study evaluated the hypothesis that Native Americans could have a greater frequency of rapid acetylators. NAT2 diversity was analyzed in several native populations, many of them never studied before for this gene. A total of 233 individuals from 14 populations [Native Americans: Apalaí (n = 35), Arara (n = 10), Gavião (n= 7), Guarani (n = 34), Jamamadi (n = 1), Lengua (n = 22), Suruí (n = 4), Wai-wai (n = 15), Xavante (n = 2), Zoró (n = 8), Totonaco (n = 8); Native Asians: Siberian Eskimo (n = 38); Mexican mestizos (n = 34); Africans (n = 15)] were sequenced for the exon 2 of the NAT2 gene. Seven known polymorphisms were observed at positions 191 (G>A), 282 (C>T), 341 (T>C), 481 (C>T), 590 (G>A), 803 (A>G), and 857 (G>A), which lead to the formation of 12 haplotypes. These could be grouped in rapid (27.5%), slow (70.0%) acetylators, and 2.5% not determined (the haplotypes were not yet speci cally related to phenotypes). When the populations were separately analyzed, Siberian Eskimo, mestizo Mexicans, and Africans showed a higher prevalence of slow acetylators, as compared to Native Americans, the diference between the two groups being statistically signi cant (p = 0.04399). It is noteworthy that the frequency of the slow phenotype is very high around the world (well above 50%). It is possible that the high prevalence of rapid acetylators in Native Americans could be related to their environment, and more speci cally to the xenobiotics found in it.