{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T04:13:10Z","timestamp":1782187990899,"version":"3.54.5"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Tolerance to thiopurine drugs is modulated by polymorphisms in the TPMT and NUDT15 pharmacogenes, affecting the activity of the encoded TPMT and NUDT15 enzymes. A recent study disclosed a significant impact of the NUDT15 rs147390019 single nucleotide variant (SNV) on thiopurine tolerance in acute lymphoblastic leukemia patients, self-identified as Hispanic\/Latino. Native American (Amerindigenous) ancestry accounts almost exclusively for the presence of rs147390019 in Admixed Americans. We assessed the impact of rs147390019 (NUDT15*4) on the genotype-predicted risk of thiopurine intolerance in three Indigenous cohorts from reservation areas in the Brazilian Amazon, namely Munduruku (n = 77), Paiter-Suru\u00ed (n = 81) and Yanomami (n = 90).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The individuals were genotyped using a panel of ancestry-informative markers and a validated TaqMan assay for the rs147390019 polymorphism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The median proportion of Native ancestry in the cohorts was &amp;gt;99%. The rs147390019 SNP was not detected in Yanomami, but was present in Munduruku and Paiter-Suru\u00ed at the highest frequencies reported worldwide (0.130 and 0.191, respectively). Carriage of rs147390019 had a major effect on the distribution of inferred NUDT15 and combined NUDT15\/TPMT metabolic phenotypes, such that the CPIC guideline recommendations for thiopurine dosing adjustments would apply to 29.9% and 70.4% of the Munduruku and Paiter-Suru\u00ed cohorts, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The results provide strong evidence to support inclusion of rs147390019 in pharmacogenetic testing panels to guide thiopurine dosing adjustments in Native and Latin American populations, acknowledging their ample genetic diversity and underrepresentation in pharmacogenetic research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1804744","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:37:04Z","timestamp":1773758224000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Distribution of NUDT15*4 in Native American populations of the Brazilian Amazon and risk of intolerance to thiopurine drugs"],"prefix":"10.3389","volume":"17","author":[{"given":"Guilherme","family":"Suarez-Kurtz","sequence":"first","affiliation":[{"name":"Divis\u00e3o de Pesquisa Cl\u00ednica e Desenvolvimento Tecnol\u00f3gico, Instituto Nacional de C\u00e2ncer (INCA)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Beatriz Ribeiro","family":"Elias","sequence":"additional","affiliation":[{"name":"Divis\u00e3o de Pesquisa Cl\u00ednica e Desenvolvimento Tecnol\u00f3gico, Instituto Nacional de C\u00e2ncer (INCA)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Alex","family":"Carvaho","sequence":"additional","affiliation":[{"name":"Instituto Federal do Rio de Janeiro (IFRJ)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Dias","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Diagn\u00f3stico por DNA (LDD), Universidade do Estado do Rio de Janeiro (UERJ)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonor","family":"Gusm\u00e3o","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Diagn\u00f3stico por DNA (LDD), Universidade do Estado do Rio de Janeiro (UERJ)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Cesar","family":"Basta","sequence":"additional","affiliation":[{"name":"Departamento de Endemias Samuel Pessoa, Escola Nacional de Sa\u00fade P\u00fablica, Funda\u00e7\u00e3o Oswaldo Cruz (ENSP\/Fiocruz)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamila Alessandra","family":"Perini","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa de Ci\u00eancias Farmac\u00eauticas (LAPESF), Universidade do Estado do Rio de Janeiro (UERJ)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"9222","DOI":"10.3390\/ijerph18179222","article-title":"Mercury exposure in Munduruku indigenous communities from Brazilian amazon: methodological background and an overview of the principal results","volume":"18","author":"Basta","year":"2021","journal-title":"Int. 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