Unraveling CYP2E1 haplotypes in alcoholics from Central Brazil: A comparative study with 1000 genomes population.

We evaluated genetic variability of single nucleotide polymorphisms (SNPs) situated in the CYP2E1 gene promoter in alcoholics. We also compared 1000 Genomes Project of CYP2E1 polymorphisms with frequencies of genotypes and haplotypes. Eight variation points were exclusively found in Brazilians. The allelic distributions of the rs3813867, rs2031920 and rs2031921 polymorphisms in the CYP2E1 showed that the wild alleles (G, C, T, respectively) had higher frequencies in both groups, alcoholic (96%, 96%, 96%) and a control group (95.8%, 94.9%, 94.9%), when compared to the mutated allele (C, T, C, respectively). The variation points, rs3813867, rs2031920 and rs2031921 showed strong linkage disequilibrium (LOD ≥ 2, D ' = 1). South Asian populations presented larger LD blocks compared to the other populations. Our results showed that the allelic frequencies were markedly different among ethnicities and have contributed to the knowledge regarding the distribution among ethnic groups, being associated to alcohol consumption worldwide.

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

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.