RESPONSE TO ALCOHOL IN ASIAN MEN AND WOMEN

申请者摘要：作为一个整体，亚洲人的酒精率较低 虐待和酒精依赖比大多数其他族裔群体都要多。这 酒精中毒风险的降低被认为是由于以下几种因素的共同作用 生物和社会文化因素。在生物领域，最近 研究的重点是遗传决定因素的作用，如 作为酒精代谢酶的多态，酒精 脱氢酶(ADH)和乙醛脱氢酶(ALDH)，负责 酒精引起的潮红，酒精和乙醛的差异 退化，以及观察到的发病率的一些种族差异 酗酒。然而，几乎没有关于这些问题的信息 酶的多态实际上会影响一个人的饮酒行为 或者社会文化变量如何与这些生物因素相互作用 变量。飞行员数据表明，一些亚洲人可能会经历一场 在质量上，甚至在数量上，对酒精的不同反应。 还需要更多的研究来评估具体的影响 酒精代谢酶的多态性及其相互作用 关于个体对酒精的反应的社会文化变量。这 项目将使用组间、重复测量设计进行测试 男性和女性对安慰剂和酒精管理的反应 具有不同ADH2、ADH3和ALDH2基因的亚洲血统。这 研究将重点放在酒精和酒精反应的各种指标上 新陈代谢。对酒精反应的衡量标准将包括主观的 醉酒感觉，心率，血压，脸红， 面部血流量，血浆皮质醇和ACTH水平，以及脑电测量。 酒精新陈代谢将通过血液酒精浓度来衡量 (BACS)和乙醛水平。社会文化变量(例如，特定 亚裔种族，生活在美国的几代人，以及 融入美国社会的程度)，可能的因素 间接影响对酒精的反应，或者通过不同的水平 酒精经验或通过习得的反应(例如，文化 对饮酒的态度或对酒精影响的预期)也会 被评估。假设携带ALDH2*2等位基因的个体 会表现出与受试者相比对酒精的更强反应 仅有ALDH2*1等位基因。它还假设，独立于 ALDH2*2等位基因、携带ADH2*2和ADH3*1等位基因的受试者将拥有更多 ADH2*1和ADH3*2受试者对酒精的强烈反应 等位基因。这项研究还将分析数据，以此来检验 亚洲女性对酒精的反应与亚洲男性不同， 为了确定社会文化因素是否可以解释 酒精敏感性，并探索可能的调解和缓和 与酒精中毒和酒精浓度相关的变量 消费模式。这项拟议的研究是努力的一部分 阐明了由基因决定的对酒精的反应 有可能提供关键信息以了解ADH和 ALDH基因可能会与其他重要的变量相互作用来修改 亚洲男性饮酒和防止酗酒的研究 女人。

APPLICANT'S ABSTRACT: Asians, as a whole, have lower rates of alcohol abuse and alcohol dependence than most other ethnic groups. This decreased risk for alcoholism is thought to result from a combination of biological and sociocultural factors. In the biological realm, recent research has focused on the role of genetically determined factors, such as polymorphisms of the alcohol metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), as responsible for alcohol-induced flushing, differences in alcohol and acetaldehyde degradation, and some of the observed ethnic differences in the incidence of alcoholism. There is little information, however, about how these enzyme polymorphisms actually influence an individual's drinking behavior or how sociocultural variables might interact with these biological variables. Pilot data suggest that some Asians may experience a qualitatively, and perhaps quantitatively, different reaction to alcohol. Additional research is needed to evaluate the impact of specific polymorphisms of the alcohol metabolizing enzymes and their interaction with sociocultural variables on individual response to alcohol. This project will use a between-group, repeated measures design to test response to both placebo and alcohol administration among men and women of Asian heritage with different ADH2, ADH3, and ALDH2 genotypes. This study will focus on various measures of reaction to alcohol and alcohol metabolism. Measures of reaction to alcohol will include subjective feelings of intoxication, heart rate, blood pressure, facial flushing, facial blood flow, plasma cortisol and ACTH levels, and EEG measures. Alcohol metabolism will be measured by blood alcohol concentrations (BACS) and acetaldehyde levels. Sociocultural variables (e.g., specific Asian ethnicity, number of generations lived in the United States, and level of acculturation into American society), factors that may indirectly affect response to alcohol, either through differential levels of experience with alcohol or through learned responses (e.g., cultural attitudes toward drinking or expectations of alcohol's effects) will also be assessed. It is hypothesized that individuals with ALDH2*2 alleles will demonstrate enhanced responses to alcohol compared with subjects with only ALDH2*1 alleles. It is also hypothesized that, independent of ALDH2*2 alleles, subjects with ADH2*2, and ADH3*1 alleles will have more intense responses to alcohol than subjects with ADH2*1 and ADH3*2 alleles. This study will also analyze data as a way to examine whether the response to alcohol of Asian women differs from that of Asian men, to determine if sociocultural factors explain some of the variability in alcohol sensitivity, and to explore possible mediating and moderating variables associated with intensity of alcohol intoxication and alcohol consumption patters. The proposed research is part of an effort to elucidate genetically determined responses to alcohol and has the potential to provide critical information for understanding how ADH and ALDH genes might interact with other important variables to modify alcohol drinking and protection from alcoholism among Asian men and women.