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Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil

INTRODUCTION: 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...

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Autores principales: Rodrigues, Juliana Carla Gomes, de Souza, Tatiane Piedade, Pastana, Lucas Favacho, Ribeiro dos Santos, André Maurício, Fernandes, Marianne Rodrigues, Pinto, Pablo, Wanderley, Alayde Vieira, de Souza, Sandro José, Kroll, José Eduardo, Pereira, Adenilson Leão, Magalhães, Leandro, Mercês, Laís Reis das, Vidal, Amanda Ferreira, Vinasco-Sandoval, Tatiana, Cavalcante, Giovanna Chaves, Guerreiro, João Farias, de Assumpção, Paulo Pimentel, Ribeiro-dos-Santos, Ândrea, Santos, Sidney, dos Santos, Ney Pereira Carneiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159207/
https://www.ncbi.nlm.nih.gov/pubmed/32294118
http://dx.doi.org/10.1371/journal.pone.0231651
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author Rodrigues, Juliana Carla Gomes
de Souza, Tatiane Piedade
Pastana, Lucas Favacho
Ribeiro dos Santos, André Maurício
Fernandes, Marianne Rodrigues
Pinto, Pablo
Wanderley, Alayde Vieira
de Souza, Sandro José
Kroll, José Eduardo
Pereira, Adenilson Leão
Magalhães, Leandro
Mercês, Laís Reis das
Vidal, Amanda Ferreira
Vinasco-Sandoval, Tatiana
Cavalcante, Giovanna Chaves
Guerreiro, João Farias
de Assumpção, Paulo Pimentel
Ribeiro-dos-Santos, Ândrea
Santos, Sidney
dos Santos, Ney Pereira Carneiro
author_facet Rodrigues, Juliana Carla Gomes
de Souza, Tatiane Piedade
Pastana, Lucas Favacho
Ribeiro dos Santos, André Maurício
Fernandes, Marianne Rodrigues
Pinto, Pablo
Wanderley, Alayde Vieira
de Souza, Sandro José
Kroll, José Eduardo
Pereira, Adenilson Leão
Magalhães, Leandro
Mercês, Laís Reis das
Vidal, Amanda Ferreira
Vinasco-Sandoval, Tatiana
Cavalcante, Giovanna Chaves
Guerreiro, João Farias
de Assumpção, Paulo Pimentel
Ribeiro-dos-Santos, Ândrea
Santos, Sidney
dos Santos, Ney Pereira Carneiro
author_sort Rodrigues, Juliana Carla Gomes
collection PubMed
description INTRODUCTION: 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.
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spelling pubmed-71592072020-04-22 Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil Rodrigues, Juliana Carla Gomes de Souza, Tatiane Piedade Pastana, Lucas Favacho Ribeiro dos Santos, André Maurício Fernandes, Marianne Rodrigues Pinto, Pablo Wanderley, Alayde Vieira de Souza, Sandro José Kroll, José Eduardo Pereira, Adenilson Leão Magalhães, Leandro Mercês, Laís Reis das Vidal, Amanda Ferreira Vinasco-Sandoval, Tatiana Cavalcante, Giovanna Chaves Guerreiro, João Farias de Assumpção, Paulo Pimentel Ribeiro-dos-Santos, Ândrea Santos, Sidney dos Santos, Ney Pereira Carneiro PLoS One Research Article INTRODUCTION: 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. Public Library of Science 2020-04-15 /pmc/articles/PMC7159207/ /pubmed/32294118 http://dx.doi.org/10.1371/journal.pone.0231651 Text en © 2020 Rodrigues et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Rodrigues, Juliana Carla Gomes
de Souza, Tatiane Piedade
Pastana, Lucas Favacho
Ribeiro dos Santos, André Maurício
Fernandes, Marianne Rodrigues
Pinto, Pablo
Wanderley, Alayde Vieira
de Souza, Sandro José
Kroll, José Eduardo
Pereira, Adenilson Leão
Magalhães, Leandro
Mercês, Laís Reis das
Vidal, Amanda Ferreira
Vinasco-Sandoval, Tatiana
Cavalcante, Giovanna Chaves
Guerreiro, João Farias
de Assumpção, Paulo Pimentel
Ribeiro-dos-Santos, Ândrea
Santos, Sidney
dos Santos, Ney Pereira Carneiro
Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil
title Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil
title_full Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil
title_fullStr Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil
title_full_unstemmed Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil
title_short Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil
title_sort identification of nudt15 gene variants in amazonian amerindians and admixed individuals from northern brazil
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159207/
https://www.ncbi.nlm.nih.gov/pubmed/32294118
http://dx.doi.org/10.1371/journal.pone.0231651
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