Toxicogenetics Of Alcohol

长期过量饮酒会对肝脏、大脑、心脏和胰腺等主要器官系统产生各种毒性影响。个体对长期过量饮酒的毒性反应似乎是不同的，受遗传和环境因素的调节。这种关系可能是双向的，酒精使用模式和毒性反应的因素都起作用。目前，有很好的证据表明中枢5-羟色胺能功能映射到功能性5-羟色胺转运体多态(5HTTLPR)可能与神经毒性反应的差异有关，而在外围，血管紧张素转换酶(ACE)内含子16插入/缺失多态与酒精性心肌病的不同风险相关。这项工作的目的是确定5HTTLPR是否与酗酒模式有关，以及5HTTLPR和ACE是否与酒精中毒有关，从而导致心脏信号动力学和心功能的改变。我们目前有100个人的酒精使用模式和基因型数据，目标是250名受试者，并计划对酒精依赖的受试者进行研究，以确定包括酒精使用模式在内的哪些因素可能与心血管功能障碍有关。这一努力将为今后旨在阐明这种毒性的机制的工作奠定基础，同时为制定旨在查明弱势人口和降低风险的干预措施提供基础。

Chronic excessive alcohol use is associated with a variety of toxic effects on major organ systems such as liver, brain, heart and pancreas. The individual toxic response to chronic excessive alcohol use appears to be heterogeneous, mediated by genetic and environmental factors. This relationship may be bidirectional, with factors contributing to both patterns of alcohol use as well as toxic responses. At present, there is good evidence that central serotonergic function mapping unto the functional serotonin transporter polymorphism (5HTTLPR) may be associated with differences in neurotoxic response, while peripherally, the angiontensin converting enzyme (ACE) insertion/deletion polymorphism at intron 16 is associated with a differential risk for alcoholic cardiomyopathy. The purpose of this work is to determine if 5HTTLPR is associated with a binge-drinking pattern and if 5HTTLPR and ACE are associated with alcohol toxicity resulting in altered cardiac signal dynamics and heart function. We currently have alcohol use pattern and genotype data from 100 individuals, with a target of 250 subjects and are planning to study subjects with alcohol dependence to determine what factors including alcohol use pattern may be associated with cardiovascular dysfunction. This effort will provide a foundation for future work aimed at elucidating a mechanism for this toxicity while providing a basis for the development of interventions aimed at identifying vulnerable populations and reducing risk.