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首页> 外文期刊>Alcohol >DNA damage in peripheral blood lymphocytes and association with polymorphisms in the promoter region of the CYP2E1 gene in alcoholics from Central Brazil
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DNA damage in peripheral blood lymphocytes and association with polymorphisms in the promoter region of the CYP2E1 gene in alcoholics from Central Brazil

机译：外周血淋巴细胞的DNA损伤和巴西中央CYP2E1基因CYP2E1基因启动子区的多态性联合

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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. (C) 2016 Elsevier Inc. All rights reserved.
机译：研究了由CYP2E1酶介导的乙醇生物转化生物产物中产生的生物产物积累引起的DNA损伤。为了评估外周血淋巴细胞中的DNA损伤和CYP2E1基因的启动子区中的多态性，我们进行了案例对照研究，包括75个酗酒者和59名在社会上消耗酒精的人。之前，酗酒者以巴西中部地区戈亚尼亚市（Goiaia）市诊断出来诊断出来的心理科医疗中心酒精和药物（CAPS A / D）。彗星测定评估DNA损伤。通过Sanger测序进行CYP2E1基因的启动子区域中的RS3813867，RS2031920和RS2031921的多态性分析。 35岁的男子是最常见的酗酒者。与对照组相比，我们发现壳体组中的DNA损伤增加了（P <0.001）。与纯合非突变等位基因的个体相比，在RS3813867，RS2031920和RS2031921多态性中杂合的酗酒表现出更高的DNA损伤（尾长和橄榄尾矩）。以前的研究表明，CYP2E1基因的启动子区中的多态性可能导致较高的CYP2E1转录活性，与非流体相比增加酶活性，表明突变等位基因（杂合或纯合）的存在可能与较高的醇代谢速率相关因此，醇消耗后显示乙醛水平增加，然后可以发挥其致癌作用。 （c）2016年Elsevier Inc.保留所有权利。

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