Toxicogenetics Of Alcohol

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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.