{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:32:24Z","timestamp":1790818344125,"version":"4.1.0"},"reference-count":16,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p>\n                           <jats:italic toggle=\"yes\">TPMT<\/jats:italic> and <jats:italic toggle=\"yes\">NUDT15<\/jats:italic> polymorphisms are major determinants of tolerance to thiopurine drugs used in leukemias and nonmalignant immunologic disorders. We adopted an extreme discordant phenotype approach to explore the impact of Native American versus European ancestry on the distribution of <jats:italic toggle=\"yes\">TPMT<\/jats:italic> and <jats:italic toggle=\"yes\">NUDT15<\/jats:italic> polymorphisms, and inferred metabolic phenotypes in the 1000 Genomes Ad Mixed American superpopulation. Significant differences were observed in the distribution of <jats:italic toggle=\"yes\">TPMT<\/jats:italic> and <jats:italic toggle=\"yes\">NUDT15<\/jats:italic> haplotypes (star alleles) between individuals with predominant (&gt;70%) European versus Native ancestry. The largest difference is related to <jats:italic toggle=\"yes\">NUDT15<\/jats:italic> rs116855232. Based on the combined TPMT\/NUDT15 metabolic phenotypes, the Clinical Pharmacogenetics Implementation Consortium recommendations for thiopurine dose adjustment applies to 40.1% of individuals with major Native American ancestry, compared to 12.8% of individuals with predominantly European ancestry. These findings may be relevant to the adoption and interpretation of pharmacogenetic tests for thiopurine drugs across Latin America peoples with different European and Native-American ancestries.<\/jats:p>","DOI":"10.1097\/fpc.0000000000000388","type":"journal-article","created":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T05:11:37Z","timestamp":1571980297000},"page":"1-4","source":"Crossref","is-referenced-by-count":11,"title":["Pharmacogenomics implications of population diversity in Latin America: TPMT and NUDT15 polymorphisms and thiopurine dosing"],"prefix":"10.1097","volume":"30","author":[{"given":"Guilherme","family":"Suarez-Kurtz","sequence":"first","affiliation":[{"name":"Coordena\u00e7\u00e3o de Pesquisa, Instituto Nacional do C\u00e2ncer"},{"name":"Rede Nacional de Farmacogen\u00e9tica, Rio de Janeiro"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilderlanio Santana de","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Gen\u00e9tica e Biologia Molecular, Universidade Federal do Par\u00e1, Bel\u00e9m"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro Jos\u00e9","family":"de Sousa","sequence":"additional","affiliation":[{"name":"Instituto do C\u00e9rebro, Universidade Federal do Rio Grande do Norte"},{"name":"BioME, Instituto Metr\u00f3pole Digital, Universidade Federal do Rio Grande do Norte, Natal, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-20230915","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation.","volume":"526","year":"2015","journal-title":"Nature"},{"key":"R2-20230915","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1002\/cpt.1322","article-title":"Standardized biogeographic grouping system for annotating populations in pharmacogenetic research.","volume":"105","author":"Huddart","year":"2019","journal-title":"Clin Pharmacol Ther"},{"key":"R4-20230915","doi-asserted-by":"crossref","first-page":"e1004572","DOI":"10.1371\/journal.pgen.1004572","article-title":"Admixture in Latin America: geographic structure, phenotypic diversity and self-perception of ancestry based on 7,342 individuals.","volume":"10","author":"Ruiz-Linares","year":"2014","journal-title":"Plos Genet"},{"key":"R5-20230915","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1002\/cpt.1304","article-title":"Clinical Pharmacogenetics Implementation Consortium guideline for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 update.","volume":"105","author":"Relling","year":"2019","journal-title":"Clin Pharmacol Ther"},{"key":"R6-20230915","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1101\/gr.094052.109","article-title":"Fast model-based estimation of ancestry in unrelated individuals.","volume":"19","author":"Alexander","year":"2009","journal-title":"Genome Res"},{"key":"R7-20230915","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.2217\/pgs.15.73","article-title":"Genome-wide association study of warfarin maintenance dose in a Brazilian sample.","volume":"16","author":"Parra","year":"2015","journal-title":"Pharmacogenomics"},{"key":"R8-20230915","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1002\/cpt.1268","article-title":"Pharmacogene variation consortium gene introduction: NUDT15","volume":"105","author":"Yang","year":"2019","journal-title":"Clin Pharmacol Ther"},{"key":"R9-20230915","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/ajpa.21270","article-title":"Genetic make up and structure of Colombian populations by means of uniparental and biparental DNA markers.","volume":"143","author":"Rojas","year":"2010","journal-title":"Am J Phys Anthropol"},{"key":"R10-20230915","doi-asserted-by":"crossref","first-page":"e17063","DOI":"10.1371\/journal.pone.0017063","article-title":"The genomic ancestry of individuals from different geographical regions of Brazil is more uniform than expected.","volume":"6","author":"Pena","year":"2011","journal-title":"Plos One"},{"key":"R11-20230915","doi-asserted-by":"crossref","first-page":"11422","DOI":"10.1038\/s41598-018-29851-3","article-title":"Exploring Cuba's population structure and demographic history using genome-wide data.","volume":"8","author":"Fortes-Lima","year":"2018","journal-title":"Sci Rep"},{"key":"R12-20230915","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1002\/cpt.1379","article-title":"NUDT15 polymorphism in native American populations of Brazil.","volume":"105","author":"Suarez-Kurtz","year":"2019","journal-title":"Clin Pharmacol Ther"},{"key":"R13-20230915","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/cpt.299","article-title":"The value of routine pharmacogenomic screening-are we there yet? A perspective on the costs and benefits of routine screening-shouldn't everyone have this done?","volume":"99","author":"Veenstra","year":"2016","journal-title":"Clin Pharmacol Ther"},{"key":"R14-20230915","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1002\/cpt.1030","article-title":"Economics of pharmacogenetic-guided treatments: underwhelming or overstated?","volume":"103","author":"Hughes","year":"2018","journal-title":"Clin Pharmacol Ther"},{"key":"R15-20230915","doi-asserted-by":"crossref","DOI":"10.1002\/pbc.26871","article-title":"An investigation of toxicities and survival in Hispanic children and adolescents with ALL: results from the Dana-Farber Cancer Institute ALL Consortium protocol 05-001","volume":"65","author":"Kahn","year":"2018","journal-title":"Pediatr Blood Cancer"},{"key":"R16-20230915","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1038\/s41436-019-0448-7","article-title":"Impact of NUDT15 genetics on severe thiopurine-related hematotoxicity in patients with European ancestry.","volume":"21","author":"Schaeffeler","year":"2019","journal-title":"Genet Med"},{"key":"R17-20230915","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1111\/bjh.14532","article-title":"TPMT and NUDT15 genes are both related to mercaptopurine intolerance in acute lymphoblastic leukaemia patients from Uruguay.","volume":"181","author":"Soler","year":"2018","journal-title":"Br J Haematol"}],"container-title":["Pharmacogenetics and Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/FPC.0000000000000388","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T01:02:04Z","timestamp":1694739724000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/FPC.0000000000000388"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1]]},"references-count":16,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020]]}},"URL":"https:\/\/doi.org\/10.1097\/fpc.0000000000000388","relation":{},"ISSN":["1744-6872"],"issn-type":[{"value":"1744-6872","type":"print"}],"subject":[],"published":{"date-parts":[[2020,1]]}}}