Avaliação do dano ao DNA pelo ensaio cometa e análise dos pontos de variação dos genes CYP2E1, CYP1A1 e OGG1 em etilistas do município de Goiânia-GO

Abstract

Ethanol is considered the most consumed drug in the world, is part of several cultures. However, chronic ethanol consumption has become a social and public health problem, since it has serious health consequences and is a risk factor for several diseases and mortality. The CYP2E1 gene encodes an enzyme that is the main constituent of the microsomal oxidation system of ethanol. The CYP1A1 gene encodes an enzyme that, like CYP2E1, acts on the oxidative biotransformation of phase I substrates of the metabolism of xenobiotics such as ethanol. In addition, genes related to DNA repair such as OGG1 are also of great importance as they are involved in protecting the genome by helping to maintain the cellular functions of organisms. Problems in the repair process can interfere with aging and promote disease development. Genetic variations in these genes result in significant differences in enzyme activity. However, there is still no clear correlation between the functional significance of these variations in both ethanol metabolism and ethylene repair. In the present study, the variability of specific regions of the CYP2E1, CYP1A1 and OGG1 genes were analyzed in samples of alcoholics from a Psychosocial Care Center (CAPS) of the State of Goiás, in the city of Goiânia, and the results were compared with the data obtained by the 1000Genomas project. A study of the association between the polymorphism of these genes and the damage to the DNA in ethanol was carried out. Sequencing reactions and the comet assay were performed. There was no relation between the data of the polymorphism found with DNA damage. However, in the analysis of the DNA damage between the case and control groups, greater damage was observed in the alcoholics in relation to the control group. The genotypic frequencies adhered to that expected by the HardyWeinberg Equilibrium for all the polymorphism in the Brazilian samples. Based on the polymorphism of the CYP2E1 gene, 15 haplotypes were inferred. Of these, only 4 haplotypes were common in all populations. While based on the two polymorphism of the CYP1A1 and OGG1 genes, 3 haplotypes were inferred for each gene, all present in the Brazilian study population.