Variabilidade do gene CYP2D6 em populações ameríndias

Abstract

The genetic cytochrome P450 superfamily is of significant relevance to the process of metabolizing drugs in the human liver. The CYP2D6 gene, one of the most studied genes due to its vast amount of genomic variations and the low influence of external non-genetic factors that affect the metabolization process of more than 20% of the drugs marketed. The molecular profile of the CYP2D6 gene influences several classes of drugs: antidepressants, antipsychotics, antiarrhythmics, opioid analgesics, anticancer agents among other drugs. However, these protocols are designed mainly for populations of European origin, not being properly employed in Brazilian populations, as are results from a complex process of miscegenation involving the contribution mainly from European, African and Amerindian. Pharmacogenomic studies in Amerindian populations are scarce. Thus, in the absence of consistent data, the establishment of public health policies aimed at the implementation of precision medicine in these populations, and in peoples mixed with these ethnic groups, is impaired. Genomic studies capable of analyzing the genetic heterogeneity of biomarkers associated with the metabolism process of several drugs in Amerindian and mixed populations are of great scientific impact. Based on this study evaluated the molecular profile 22 therapy important predictors of the CYP2D6 gene polymorphisms in individuals in American Indians Amazon samples from three tribes: the Asurini Trocará, Asurini Koatinemo and the Kayapo-Xikrin. The DNA was extracted from the peripheral blood of the individuals studied. Polymorphism genotypes were performed by Taqman® assays in OpenArray® on the QuantStudio ™ 12K Flex Real-Time PCR System. The statistical analyses was due in the programs Arlequin v. 3.5.2.2, SPSS v. 12.0 and the statistical package of R. In addition to this original work, a review was carried out to group CYP2D6 gene data in other Amerindian populations. From the results it was possible to observe that the normal extensive metabolism profile is the most frequent in the Amerindian population of the review and in the Brazilian Amazon Amerindian population. The profiles of clinical importance, slow and ultrafast, presented low frequency in the populations of the review and was not observed in the Amazonian population. These data may infer that the Amerindian population may have some protection from drug-related adverse effects and drug failure that are metabolized by CYP2D6.