Short CommunicationPharmacogenomics of thiopurines: distribution of TPMT and NUDT15 polymorphisms in the Brazilian AmazonFerreira, Guilherme Motta Antunesa,,b; Ribeiro Elias, Anna Beatrizc; Nascimento, Joabia,,d; Monteiro, Wuelton Marceloa,,d; Melo, Gisely Cardosoa,,d; Baia-da-Silva, Djane Clarysa,,d; Lacerda, Marcus Vinícius Guimarãesa,,d,,e; Suarez-Kurtz, GuilhermecAuthor Information aUniversidade do Estado do Amazonas bFundação de Hematologia e Hemoterapia do Amazonas, Manaus cCoordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro dFundação de Medicina Tropical Dr Heitor Vieira Dourado eInstituto Leônidas & Maria Deane, Fiocruz, Manaus, Brazil Received 16 March 2020 Accepted 27 April 2020 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.pharmacogeneticsandgenomics.com. Correspondence to Guilherme Suarez-Kurtz, MD, PhD, Centro de Pesquisa, Instituto Nacional de Câncer, Rua André Cavalcanti 37, Rio de Janeiro RJ 20231, Brazil, Tel: +55 21 3207 6552; e-mail: firstname.lastname@example.org Pharmacogenetics and Genomics: October 2020 - Volume 30 - Issue 8 - p 184-189 doi: 10.1097/FPC.0000000000000411 Buy SDC Metrics Abstract Reduced function alleles in the TPMT and NUDT15 genes are risk factors for thiopurine toxicity. This study evaluated the influence of Native ancestry on the distribution of TPMT (rs1142345, rs1800460 and rs1800462) and NUDT15 (rs116855232) polymorphisms and compound metabolic phenotypes in 128 healthy males from the Brazilian Amazon. The average proportion of Native and European ancestry differed greatly and significantly between self-declared Amerindians and non-Amerindians, although extensive admixture in both groups was evident. Native ancestry was not significantly associated with the frequency distribution of the TPMT or NUDT15 polymorphisms investigated. The apparent discrepancy with our previous results for NUDT15 rs116855232 in the Ad Mixed American superpopulation of the 1000 Genomes Project is ascribed to the diversity of the Native populations of the Americas. Based on the inferred TPMT/NUDT15 compound metabolic phenotypes, the Clinical Pharmacogenetics Implementation Consortium recommendations for starting thiopurine therapy with reduced doses or to consider dose reduction applied respectively to 3–5% and to 12–20% of the study cohorts. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.