DNA damage in peripheral blood lymphocytes and association with polymorphisms in the promoter region of the CYP2E1 gene in alcoholics from Central Brazil

Ramos, Jheneffer Sonara Aguiar; Alves, Alessandro Arruda; Lopes, Mariana Paiva; Pedroso, Thays Millena Alves; Felício, Leandro Prado; Carvalho, Wanessa Fernandes; Franco, Fernanda Craveiro; Melo, Caroline Oliveira de Araújo; Gonçalves, Macks Wendhell; Soares, Thannya Nascimento

DNA damage in peripheral blood lymphocytes and association with polymorphisms in the promoter region of the CYP2E1 gene in alcoholics from Central Brazil

Data

2016

Autores

Ramos, Jheneffer Sonara Aguiar

Alves, Alessandro Arruda

Lopes, Mariana Paiva

Pedroso, Thays Millena Alves

Felício, Leandro Prado

Carvalho, Wanessa Fernandes

Franco, Fernanda Craveiro

Melo, Caroline Oliveira de Araújo

Gonçalves, Macks Wendhell

Soares, Thannya Nascimento

Resumo

DNA damage caused by the accumulation of bio-products generated in the biotransformation of ethanol to acetaldehyde mediated by the CYP2E1 enzyme has been studied. To evaluate DNA damage in peripheral blood lymphocytes and the possible association with polymorphisms in the promoter region of the CYP2E1 gene, we performed a case-control study including 75 alcoholics and 59 individuals who consume alcohol socially. Alcoholics were previously diagnosed by the Psychosocial Care Center – Alcohol and Drugs (CAPS A/D) in the city of Goiania, Goias state, Central Brazil. DNA damage was evaluated by comet assay. The analysis of the rs3813867, rs2031920, and rs2031921 polymorphisms in the promoter region of CYP2E1 gene was performed by Sanger sequencing. Men older than 35 years old were the most common alcoholics. We found increased DNA damage in the case group, compared to the control group (p < 0.001). Alcoholics who were heterozygous in the rs3813867, rs2031920, and rs2031921 polymorphisms showed higher DNA damage (tail length and olive tail moment), compared to individuals with the homozygous non-mutated allele. Previous studies have shown that polymorphisms in the promoter region of the CYP2E1 gene could cause higher CYP2E1 transcriptional activity, increasing enzyme activity compared with nondrinkers, indicating that the presence of the mutated allele (heterozygous or homozygous) may be associated with higher alcohol metabolic rates and therefore show increased acetaldehyde levels after alcohol consumption, which then can exert its carcinogenic effect.

Palavras-chave

CYP2E1, DNA damage, Ethanol, Metabolism, Polymorphism

Citação

RAMOS, Jheneffer Sonara Aguiar et al. DNA damage in peripheral blood lymphocytes and association with polymorphisms in the promoter region of the CYP2E1 gene in alcoholics from Central Brazil. Alcohol, Amsterdan, v. 57, p. 35-39, 2016. DOI: 10.1016/j.alcohol.2016.08.007. Disponível em: https://www.sciencedirect.com/science/article/pii/S0741832916301550. Acesso em 30 ago. 2023.