Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil.
<h4>Introduction</h4>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 c...
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Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0231651 |
| _version_ | 1818362269288890368 |
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| author | Juliana Carla Gomes Rodrigues Tatiane Piedade de Souza Lucas Favacho Pastana André Maurício Ribeiro Dos Santos Marianne Rodrigues Fernandes Pablo Pinto Alayde Vieira Wanderley Sandro José de Souza José Eduardo Kroll Adenilson Leão Pereira Leandro Magalhães Laís Reis das Mercês Amanda Ferreira Vidal Tatiana Vinasco-Sandoval Giovanna Chaves Cavalcante João Farias Guerreiro Paulo Pimentel de Assumpção Ândrea Ribeiro-Dos-Santos Sidney Santos Ney Pereira Carneiro Dos Santos |
| author_facet | Juliana Carla Gomes Rodrigues Tatiane Piedade de Souza Lucas Favacho Pastana André Maurício Ribeiro Dos Santos Marianne Rodrigues Fernandes Pablo Pinto Alayde Vieira Wanderley Sandro José de Souza José Eduardo Kroll Adenilson Leão Pereira Leandro Magalhães Laís Reis das Mercês Amanda Ferreira Vidal Tatiana Vinasco-Sandoval Giovanna Chaves Cavalcante João Farias Guerreiro Paulo Pimentel de Assumpção Ândrea Ribeiro-Dos-Santos Sidney Santos Ney Pereira Carneiro Dos Santos |
| author_sort | Juliana Carla Gomes Rodrigues |
| collection | DOAJ |
| description | <h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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. |
| first_indexed | 2024-12-13T21:29:54Z |
| format | Article |
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| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T21:29:54Z |
| publishDate | 2020-01-01 |
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| series | PLoS ONE |
| spelling | doaj.art-80247432adae42ae8572c23f313d6aa12022-12-21T23:30:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01154e023165110.1371/journal.pone.0231651Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil.Juliana Carla Gomes RodriguesTatiane Piedade de SouzaLucas Favacho PastanaAndré Maurício Ribeiro Dos SantosMarianne Rodrigues FernandesPablo PintoAlayde Vieira WanderleySandro José de SouzaJosé Eduardo KrollAdenilson Leão PereiraLeandro MagalhãesLaís Reis das MercêsAmanda Ferreira VidalTatiana Vinasco-SandovalGiovanna Chaves CavalcanteJoão Farias GuerreiroPaulo Pimentel de AssumpçãoÂndrea Ribeiro-Dos-SantosSidney SantosNey Pereira Carneiro Dos Santos<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.https://doi.org/10.1371/journal.pone.0231651 |
| spellingShingle | Juliana Carla Gomes Rodrigues Tatiane Piedade de Souza Lucas Favacho Pastana André Maurício Ribeiro Dos Santos Marianne Rodrigues Fernandes Pablo Pinto Alayde Vieira Wanderley Sandro José de Souza José Eduardo Kroll Adenilson Leão Pereira Leandro Magalhães Laís Reis das Mercês Amanda Ferreira Vidal Tatiana Vinasco-Sandoval Giovanna Chaves Cavalcante João Farias Guerreiro Paulo Pimentel de Assumpção Ândrea Ribeiro-Dos-Santos Sidney Santos Ney Pereira Carneiro Dos Santos Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil. PLoS ONE |
| 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 |
| url | https://doi.org/10.1371/journal.pone.0231651 |
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