Alcohol Response, Expectancies & ADH1B Polymorphisms

酒精反应、期望

• 批准号: 7140402
• 负责人: DENIS M MCCARTHY
• 金额: $ 11.88万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-20 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7140402
• 关键词: African American; alcohol dehydrogenase; alcoholic beverage consumption; alcoholism /alcohol abuse; aldehyde dehydrogenases; behavioral /social science research tag; behavioral genetics; clinical research; dosage; drug metabolism; expectancy; family; family genetics; genetic polymorphism; genetic susceptibility; genotype; human subject; learning; patient oriented research; pharmacogenetics; role model; substance abuse related behavior

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.

描述（由申请人提供）：已发现酒精代谢酶（ADH、ALDH）的多态性会影响酒精依赖和大量饮酒的风险。这些多态性被认为通过改变酒精代谢并影响酒精反应的个体差异来影响酒精行为。 ADH 和 ALDH 等位基因的遗传变异在不同种族群体中发生率不同。 ADH/1B*3 等位基因仅在非洲人后裔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，可以预防与酒精相关的出生缺陷。拟议的项目将测试 ADH1B*3 等位基因在非裔美国人酒精依赖风险过程中的作用。据推测，ADH1B*3 通过影响对酒精的反应水平和影响与酒精相关的学习来防止酒精依赖。将招募一百三十名非裔美国人参与者进行酒精挑战研究。将对参与者进行 ADH1B 以及其他 ADH/ALDH 多态性的基因分型。此样本量应足以获得大约 30 名具有 ADH1B*3 等位基因的参与者。在酒精挑战访视之前，将收集有关饮酒、酒精滥用/依赖症状、酒精预期、酗酒家族史以及家庭环境中酒精模型暴露的数据。拟议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。其次，测试具有 ADH1B*3 等位基因的人对酒精的预期是否存在差异。我们还将测试预期的差异是否是酒精反应和/或家庭饮酒模式差异的函数。最后，将测试中介模型，假设 ADH1B*3 等位基因对酗酒风险的保护作用是由酒精预期差异介导的。