title: DNA damage in peripheral blood lymphocytes and association with polymorphisms in the promoter region of the CYP2E1 gene in alcoholics from Central Brazil.
abstract: 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.
authors.affiliation: Programa de Pós-Graduação em Genética, Pontifícia Universidade Católica de Goiás, Goiânia, GO, Brazil; Laboratório de Radiobiologia e Mutagênese, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Jheneffer Sonara Aguiar
authors.initials: JS
authors.lastname: Ramos
authors.affiliation: Laboratório de Radiobiologia e Mutagênese, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Alessandro Arruda
authors.initials: AA
authors.lastname: Alves
authors.affiliation: Laboratório de Radiobiologia e Mutagênese, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Mariana Paiva
authors.initials: MP
authors.lastname: Lopes
authors.affiliation: Laboratório de Radiobiologia e Mutagênese, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Thays Millena Alves
authors.initials: TM
authors.lastname: Pedroso
authors.affiliation: Laboratório de Farmacologia Bioquímica e Molecular, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Leandro Prado
authors.initials: LP
authors.lastname: Felício
authors.affiliation: Laboratório de Radiobiologia e Mutagênese, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Wanessa Fernandes
authors.initials: WF
authors.lastname: Carvalho
authors.affiliation: Laboratório de Radiobiologia e Mutagênese, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Fernanda Craveiro
authors.initials: FC
authors.lastname: Franco
authors.affiliation: Núcleo de Pesquisas Replicon, Departamento de Biologia, Pontifícia Universidade Católica de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Caroline Oliveira
authors.initials: CO
authors.lastname: Araújo Melo
authors.affiliation: Laboratório de Radiobiologia e Mutagênese, Universidade Federal de Goiás, Goiânia, Goiás, Brazil; Núcleo de Pesquisas Replicon, Departamento de Biologia, Pontifícia Universidade Católica de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Macks Wendhell
authors.initials: MW
authors.lastname: Gonçalves
authors.affiliation: Laboratório de Genética e Biodiversidade, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Thannya Nascimento
authors.initials: TN
authors.lastname: Soares
authors.affiliation: Programa de Pós-Graduação em Genética, Pontifícia Universidade Católica de Goiás, Goiânia, GO, Brazil; Núcleo de Pesquisas Replicon, Departamento de Biologia, Pontifícia Universidade Católica de Goiás, Goiânia, Goiás, Brazil; Laboratório de Citogenética Humana e Genética Molecular, Secretaria Estadual da Saúde, Goiânia, GO, Brazil.
authors.forename: Aparecido Divino
authors.initials: AD
authors.lastname: da Cruz
authors.affiliation: Programa de Pós-Graduação em Genética, Pontifícia Universidade Católica de Goiás, Goiânia, GO, Brazil; Laboratório de Radiobiologia e Mutagênese, Universidade Federal de Goiás, Goiânia, Goiás, Brazil; Núcleo de Pesquisas Replicon, Departamento de Biologia, Pontifícia Universidade Católica de Goiás, Goiânia, Goiás, Brazil; Laboratório de Genética e Biodiversidade, Universidade Federal de Goiás, Goiânia, Goiás, Brazil. Electronic address: danielamelosilva@ufg.br.
authors.forename: Daniela
authors.initials: D
authors.lastname: de Melo E Silva
mesh_terms: D000328:Adult; D057229:Alcoholics; D000437:Alcoholism / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D001938:Brazil / Q000453:epidemiology; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics*; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000502:physiology; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D019392:Cytochrome P-450 CYP2E1
keywords: CYP2E1; DNA damage; Ethanol; Metabolism; Polymorphism