Navegando por Autor "Santos, André Maurício Ribeiro dos"
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Artigo Epidemiological-molecular profile of variants associated with type 2 diabetes mellitus in indigenous populations from the Brazilian Amazon(Elsevier BV, 2023-03) Monte, Natasha; Rodrigues, Juliana Carla Gomes; Vinagre, Lui Wallacy Morikawa Souza; Pastana, Lucas Favacho; Alcântara, Angélica Leite de; Leitão, Luciana Pereira Colares; Santos, André Maurício Ribeiro dos; Fernandes, Marianne Rodrigues; Santos, Andrea Kely Campos Ribeiro dos; Guerreiro, João Farias; Assumpção, Paulo Pimentel; Santos, Sidney; Souza, Sandro José de; Santos, Ney Pereira Carneiro dosAims: While lifestyle factors are strongly associated with Type 2 diabetes (T2DM), genetic characteristics also play a role. However, much of the research on T2DM genetics focuses on European and Asian populations, leaving underrepresented groups, such as indigenous populations with high diabetes prevalence, understudied. Methods: We characterized the molecular profile of 10 genes involved in T2DM risk through complete exome sequencing of 64 indigenous individuals belonging to 12 different Amazonian ethnic groups. Results: The analysis revealed 157 variants, including four exclusive variants in the indigenous population located in the NOTCH2 and WFS1 genes with a modifier or moderate impact on protein effectiveness. Furthermore, a high impact variant in NOTCH2 was also found. Additionally, the frequency of 10 variants in the indigenous group showed significant differences when compared to other global populations that were evaluated. Conclusion: Our study identified 4 novel variants associated with T2DM in the NOTCH2 and WFS1 genes in the Amazonian indigenous populations we studied. In addition, a variant with a high predicted impact in NOTCH2 was also observed. These findings represent a valuable starting point for conducting further association and functional studies, which could help to improve our understanding of the unique characteristics of this populationArtigo Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil(2020-04-15) Rodrigues, Juliana Carla Gomes; Souza, Tatiane Piedade de; Pastana, Lucas Favacho; Santos, André Maurício Ribeiro dos; Fernandes, Marianne Rodrigues; Pinto, Pablo; Wanderley, Alayde Vieira; Souza, Sandro José de; Kroll, José Eduardo; Pereira, Adenilson Leão; Magalhães, Leandro; Mercês, Laís Reis das; Vidal, Amanda Ferreira; Vinasco-Sandoval, Tatiana; Cavalcante, Giovanna Chaves; Guerreiro, João Farias; Assumpção, Paulo Pimentel de; Ribeiro-dos-Santos, Ândrea; Santos, Sidney; Santos, Ney Pereira Carneiro dosIntroduction The nudix hydrolase 15 (NUDT15) gene acts in the metabolism of thiopurine, by catabolizing its active metabolite thioguanosine triphosphate into its inactivated form, thioguanosine monophosphate. The frequency of alternative NUDT15 alleles, in particular those that cause a drastic loss of gene function, varies widely among geographically distinct populations. In the general population of northern Brazilian, high toxicity rates (65%) have been recorded in patients treated with the standard protocol for acute lymphoblastic leukemia, which involves thiopurine-based drugs. The present study characterized the molecular profile of the coding region of the NUDT15 gene in two groups, non-admixed Amerindians and admixed individuals from the Amazon region of northern Brazil. Methods The entire NUDT15 gene was sequenced in 64 Amerindians from 12 Amazonian groups and 82 admixed individuals from northern Brazil. The DNA was extracted using phenol-chloroform. The exome libraries were prepared using the Nextera Rapid Capture Exome (Illumina) and SureSelect Human All Exon V6 (Agilent) kits. The allelic variants were annotated in the ViVa® (Viewer of Variants) software. Results Four NUDT15 variants were identified: rs374594155, rs1272632214, rs147390019, andrs116855232. The variants rs1272632214 and rs116855232 were in complete linkage disequilibrium, and were assigned to the NUDT15*2 genotype. These variants had high frequencies in both our study populations in comparison with other populations catalogued in the 1000 Genomes database. We also identified the NUDT15*4 haplotype in our study populations, at frequencies similar to those reported in other populations from around the world. Conclusion Our findings indicate that Amerindian and admixed populations from northern Brazil have high frequencies of the NUDT15 haplotypes that alter the metabolism profile of thiopurines.