Prevalência dos polimorfismos da proteína NUDS15 e TPMT na Amazônia Brasileira

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. This study reported a nominal but not significant difference in the lower allele frequency between the NAT (7.7%) and non-NAT (4.2%) sub-cohorts and this quantitative discrepancy cannot be explained by the extensive native ancestry, since that analyzed sub-cohorts with ancestry> 70% vs. <30% native. Greater care should be taken with the Native American population in order not to extrapolate the pharmacogenetic data, as it is never known whether the person may be a carrier of a bad or intermediate metabolizing phenotype for TPMT or NUDT15, thus avoiding possible intoxication