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）：发现酒精代谢酶（ADH，ALDH）的多态性会影响酒精依赖和大量酒精消耗的风险。这些多态性被认为通过改变酒精的代谢并影响酒精反应的个体差异来影响酒精行为。在不同族裔群体中，ADH和ALDH等位基因的遗传变异以不同的速度发生。 ADH/1B*3等位基因仅在非洲体面和一些美国原住民群体的个体中被鉴定出来。在美洲原住民中，已经发现ADH1B*3等位基因可防止酒精依赖。在非裔美国人中，这些等位基因与酒精中毒家族史负相关，并防止与酒精有关的先天缺陷。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。假设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保护酒精依赖。将招募一百三十三十名非裔美国人参与者进行酒精挑战研究。参与者将针对ADH1B进行基因分型，以及其他ADH/ALDH多态性。该样本量应足以获得大约30个具有ADH1B*3等位基因的参与者。在酒精挑战探访之前，将收集有关酒精使用，酒精滥用/依赖症状，饮酒的家族史，酒精中毒家族史，酒精中毒家族史和暴露于家庭环境中的饮酒。拟议的项目具有四个主要目标。一种是测试ADH1B*3等位基因是否与非裔美国人对酒精反应的增加有关。其次，测试患有ADH1B*3等位基因的人的酒精期望值是否有所不同。我们还将测试预期差异是否是酒精反应和/或家族饮酒模型差异的函数。最后，将测试一个调解模型，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。