Pharmacogenetic testing for thiopurine drugs in Brazilian acute lymphoblastic leukemia patients

Suarez‐Kurtz, Guilherme; Almeida, C.; Chapchap, Eduardo Cerello; Schramm, Marcia; Ikoma-Coltutato, Maura Rosane Valério; Lins, Mecneide Mendes; Fonseca, Tamara Canto; Aguiar, Thais Ferraz; Emerenciano, Mariana

doi:10.1016/j.clinsp.2023.100214

Cited by 2 publications

(1 citation statement)

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“…Accordingly, on the basis of the compound NUDT15/TPMT phenotypes associated with intolerance to thiopurines, the CPIC guideline recommendations to reduce the thiopurine initial dose or to consider a dose reduction apply to 4.4% Yanomami and 5.6% Munduruku, versus 41% Paiter-Suruí. The proportion of Paiter-Suruí at risk of thiopurine intolerance seems to be three- to 4-fold higher than other populations worldwide, including non-indigenous Brazilian ALL patients ( Suarez-Kurtz et al, 2023 ). However, a nearly identical proportion (41.1%) of individuals at risk for thiopurine intolerance was reported for the above mentioned subcohort of the 1KGP_AMR superpopulation, comprising persons with >85% Native ancestry ( Suarez-Kurtz et al, 2020 ).…”

Section: Discussionmentioning

confidence: 95%

NUDT15 and TPMT polymorphisms in three distinct native populations of the Brazilian Amazon

Perini,

Basta,

Suarez-Kurtz

2024

Front. Pharmacol.

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This is the first report of the distribution of TPMT and NUDT15 single nucleotide polymorphisms and metabolic phenotypes associated with cytotoxicity of thiopurine drugs, in indigenous groups of Brazilian Amazon: Munduruku, Paiter-Suruí and Yanomami. The minor allele frequency (MAF) of NUDT15 rs116855232 did not differ significantly across the groups; TPMT rs1800462 was absent, while rs1800460 and rs1142345 were in strong linkage disequilibrium, and 10- and 30-fold more common in Paiter-Suruí. Indeed, the MAFs in Paiter-Surui (0.193 and 0.188) are the largest report globally. The distribution of combined NUDT15/TPMT metabolic phenotypes differed significantly (p < 0.0001) and largely (Cramér´s V = 0.37) across cohorts. This has important pharmacogenetic implications: the Clinical Pharmacogenetics Implementation Consortium recommendations to reduce or consider reduction of thiopurine dose applies to 4.4% Yanomami, 5.6% Munduruku, versus 41% Paiter-Suruí. The proportion of Paiter-Suruí at risk of thiopurine intolerance is 3- to 4-fold higher than any other population worldwide.

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Section: Discussionmentioning

confidence: 95%