Alcohol Response, Expectancies & ADH1B Polymorphisms

描述（由申请人提供）：已经发现酒精代谢酶（ADH， ALDH）多态性影响酒精依赖和重度饮酒的风险。这些多态性被认为是通过改变酒精的代谢来影响酒精行为，并影响酒精反应的个体差异。ADH和ALDH等位基因的遗传变异在不同的种族群体中发生率不同。ADH/1B*3等位基因仅在非洲人和一些美洲原住民群体中被发现。在美洲原住民中，ADH1B*3等位基因被发现可以防止酒精依赖。在非裔美国人中，这些等位基因与酗酒家族史呈负相关，并防止酒精相关的出生缺陷。该项目将测试ADH1B*3等位基因在非裔美国人酒精依赖风险过程中的作用。假设ADH1B*3通过影响酒精反应水平和酒精相关学习来保护酒精依赖。130名非裔美国人将被招募参加一项酒精挑战研究。参与者将进行ADH1B基因分型，以及额外的ADH/ALDH多态性。这个样本量应该足以获得大约30名ADH1B*3等位基因的参与者。在酒精挑战访问之前，将收集有关酒精使用、酒精滥用/依赖症状、酒精预期、酒精家族史和在家庭环境中接触酒精模型的数据。拟议的项目有四个主要目标。一是测试ADH1B*3等位基因是否与非裔美国人对酒精的反应增加有关。第二，测试携带ADH1B*3等位基因的人对酒精的预期是否不同。我们还将测试预期的差异是否是酒精反应和/或酒精使用的家族模型差异的函数。最后，我们将检验一个中介模型，假设ADH1B*3等位基因对酒精中毒风险的保护作用是由酒精预期差异介导的。

DESCRIPTION (provided by applicant): Polymorphisms of alcohol metabolizing enzymes (ADH, ALDH) have been found to influence risk for alcohol dependence and heavy alcohol consumption. These polymorphisms are thought to influence alcohol behavior by altering the metabolism of alcohol, and influencing individual differences in alcohol response. Genetic variants in ADH and ALDH alleles occur at different rates in different ethnic groups. ADH/1B*3 alleles have been identified only in individuals of African decent and some Native American groups. In Native Americans, ADH1B*3 alleles have been found to protect against alcohol dependence. In African Americans, these alleles are negatively associated with family history of alcoholism, and protect against alcohol-related birth defects. The proposed project will test the role of ADH1B*3 alleles in the alcohol dependence risk process in African Americans. It is hypothesized that ADH1B*3 protects against alcohol dependence by influencing level of response to alcohol, and by influencing alcohol-related learning. One-hundred and thirty African American participants will be recruited for an alcohol challenge study. Participants will be genotyped for ADH1B, as well as additional ADH/ALDH polymorphisms. This sample size should be sufficient to obtain approximately 30 participants with ADH1B*3 alleles. Data on alcohol use, alcohol abuse/dependence symptoms, alcohol expectancies, family history of alcoholism and exposure to alcohol modeling in the family environment will be collected prior to the alcohol challenge visit. The proposed project has four principal aims. One is to test whether ADH1B*3 alleles are associated with increased response to alcohol in African Americans. Second, to test whether those with ADH1B*3 alleles differ in their alcohol expectancies. We will also test whether differences in expectancies are a function of differences in alcohol response and/or familial models of alcohol use. Finally, a mediation model will be tested, hypothesizing that the protective effect of ADH1B*3 alleles on alcoholism risk is mediated by differences in alcohol expectancies.