Toxicogenetics Of Alcohol

长期过量饮酒与对主要器官系统（如肝脏、大脑、心脏和胰腺）的各种毒性作用有关。慢性过量饮酒的个体毒性反应似乎是异质性的，由遗传和环境因素介导。这种关系可能是双向的，既有酒精使用模式，也有毒性反应。目前，有很好的证据表明，中枢多巴胺能功能映射到功能性5-羟色胺转运体多态性（5 HTTLPR）可能与神经毒性反应的差异有关，而外周，血管紧张素转换酶（ACE）插入/缺失多态性内含子16与酒精性心肌病的差异风险。这项工作的目的是确定是否5 HTTLPR与酗酒模式，如果5 HTTLPR和ACE与酒精中毒导致心脏信号动力学和心脏功能改变。我们目前有来自100名个体的酒精使用模式和基因型数据，目标为250名受试者，并计划研究酒精依赖受试者，以确定哪些因素（包括酒精使用模式）可能与心血管功能障碍相关。这一努力将为今后旨在阐明这种毒性机制的工作奠定基础，同时为制定旨在查明弱势群体和减少风险的干预措施奠定基础。

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.