Prevalência de polimorfismos genéticos associados à resposta terapêutica ao clopidogrel em uma população do estado do Piauí

Abstract

Clopidogrel is a widely used antiplatelet agent in the treatment of cardiovascular disease; however, its usage can cause adverse effects, due to individual genetic variety. This variety can be explained as SNPs - single nucleotide polymorphisms - in CYP2C19 Gene, responsible for metabolizing clopidogrel, among them, CYP2C19*2 and CYP2C19*17 stood out because they result in, respectively, gain and loss of the corresponding protein function. In order to avoid adverse effects after clopidogrel usage, numerous studies have been carried out in different world populations intended to investigate in patients the SNPs CYP2C19*2 and CYP2C19*17 genotypes, before therapeutic prescription. Nevertheless, as far as it is known, there are no studies that report the frequency of these loci of pharmacogenetic interest in Piauí's population. Thus, the main goal in this study is to describe allelic, genotypical and haplotypical frequencies of CYP2C19*2 and CYP2C19*17 SNPs; furthermore, present the different related phenotypes distribution in a mixed sample collected in Piauí State. The present study was carried out from DNA from 204 samples of individuals born in two past generations within the Piaui territory. DNA samples were extracted, quantified and genotyped. The last step was performed from real-time PCR, consisting of 2.5 μL Master Mix, 0.25 μL Probe / Primers and 2.25 μL DNA. , totaling 5 μL per well. In all analyzes of the study, the significance level p <0.05 was used. All genotypical frequencies presented remained balanced according to Hardy-Weinberg equilibrium (p > 0.05). The frequency 9.6% in CYP2C19*2 and 22% in CYP2C19*17 was found. The most prevalent haplotype was the *1*1, with 68.3%, followed by *1*17 with 22.1% and *1*2 with 9.6%, which indicate that the most part of the population presents functional alleles for CYP2C19. The allelic frequencies in this study were compared to allelic frequencies of other world populations and it was noticed that regarding CYP2C19*2, significant statistic differences in Brazilian regions were not found (p > 0.05), but in Asia and Africa, these differences were noticed (p < 0.05). CYP2C19*17 presented significant differences in Brazilian amerindian population, and in Latin American, Asian and European populations (p < 0.05). The most frequent phenotypes were the normal metabolizer with 46.1%, and the fast metabolizer with 31.9%, showing that a patient's genotype can interfere in medicine metabolization. Correlation between ancestry and the number of copies of *2 and *17 (p > 0.05) was not found. The results within the study can guide public policies in favor of adverse effects prevention after clopidogrel usage in Piauí's population.