DNA damage in peripheral blood lymphocytes and association with polymorphisms in the promoter region of the CYP2E1 gene in alcoholics from Central Brazil
| Autor: | Thannya Nascimento Soares, Macks Wendhell Gonçalves, Leandro P. Felício, Caroline Oliveira de Araújo Melo, Daniela de Melo e Silva, Alessandro Arruda Alves, Wanessa Fernandes Carvalho, Jheneffer Sonara Aguiar Ramos, Aparecido Divino da Cruz, Thays Millena Alves Pedroso, Fernanda Craveiro Franco, Mariana Paiva Lopes |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male Health (social science) DNA damage 010501 environmental sciences Biology Toxicology 01 natural sciences Biochemistry 03 medical and health sciences Behavioral Neuroscience symbols.namesake chemistry.chemical_compound CYP2E1 Gene 0302 clinical medicine Humans Lymphocytes Allele Alcoholics Promoter Regions Genetic 0105 earth and related environmental sciences Sanger sequencing Polymorphism Genetic Acetaldehyde Promoter Cytochrome P-450 CYP2E1 General Medicine CYP2E1 Molecular biology Comet assay Alcoholism Neurology chemistry 030220 oncology & carcinogenesis symbols Female Brazil DNA Damage |
| Zdroj: | Alcohol (Fayetteville, N.Y.). 57 |
| ISSN: | 1873-6823 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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