Real-Time Assessment of Alcohol Use Across ALDH2 Genotypes

描述(申请人提供)：建议研究的目的是建立一种实时酒精参与评估方案，该方案将使测试乙醛脱氢酶基因ALDH2的机制途径成为可能。两种技术先进的设备，手腕经皮酒精传感器(TAS)设备和一个将由iPhone访问的网站，将被进一步开发和测试，作为对自然饮酒的实时测量。这项研究将创造两个方法学上的进步，以增加这项研究和未来研究的可行性：1)一个计算机化的程序，使用从实验室酒精会议获得的有限数量的参数从TAS数据计算BAC，以及2)一个编程为灵活且易于修改的网站，允许使用这项技术解决更多的研究问题。这些研究工具将被用来检查ALDH2基因与饮酒行为的关联。到目前为止，ALDH2是与酒精依赖关系最密切的基因。对于拥有ALDH2*2等位基因导致饮酒率和问题减少的过程，已经假设了一种机械途径，但到目前为止，仅有横断面和实验室数据支持这一途径。目前的研究建议通过对携带一个ALDH2*2等位基因的个体与没有ALDH2*2等位基因的个体的实时饮酒行为进行生态有效的评估，来测试这一假设的途径。参与者将是36名亚裔美国人的子集，他们参与了之前的一项研究，因此在基因类型、酒精表型和其他相关变量方面已经有了很好的特征。每个参与者都将在实验室的酒精挑战中接受评估，以校准TAS设备，然后佩戴该设备，并在接下来的两周内使用iPhone和网站记录对酒精的反应。所获得的数据将被用来显示可行性，并确定ALDH2*2的效应大小和未来更大规模研究所需的样本量。此外，关于ALDH2*2影响的实质性假设将在这个试点样本中进行初步检验。据推测，携带ALDH2*2等位基因的人饮酒后对酒精的主观反应水平与没有这种保护性等位基因的人相似，但饮酒率、BAC和负面后果较低。研究可行性将使用一系列客观(例如，错过评估的百分比)和主观(例如，自我监控对行为的感知效果)衡量标准进行评估。多水平模型将用于同时估计人内(例如，BAC、对酒精的反应)和人与人之间(例如，ALDH2基因)的数据。这些两级和三级模型将比较不同基因类型的使用模式、BAC、主观反应和负面后果，以确定效果大小。这项研究将提高我们测量实时酒精参与的能力，并提高我们对基因变异如何影响饮酒行为、对酒精的反应以及与酒精相关问题的发展的理解。 公共卫生相关性：这项研究将推进收集实时饮酒行为的前瞻性、生态有效性评估的方法学技术。通过应用这些方法学上的进步，拟议中的研究将加强我们对基因变异如何影响饮酒行为、对酒精的反应以及与酒精相关问题的发展的理解。

DESCRIPTION (provided by applicant): The purpose of the proposed study is to establish a real-time alcohol involvement assessment protocol that will make it possible to test the mechanistic pathway of the aldehyde dehydrogenase gene ALDH2. Two technologically advanced devices, a wrist transdermal alcohol sensor (TAS) device and a website that will be accessed by an iPhone, will be further developed and tested as real-time measures of naturalistic drinking. Two methodological advancements will be created in this study to increase the feasibility of this research and of future studies: 1) a computerized program to calculate BACs from TAS data using a limited number of parameters obtained from a laboratory alcohol session, and 2) a website programmed to be flexible and easily modifiable, allowing for additional research questions to be addressed using this technology. These research tools will be used to examine the association of the ALDH2 gene with drinking behaviors. To date, ALDH2 is the gene most strongly associated with alcohol dependence. A mechanistic pathway has been hypothesized for the process by which possession of an ALDH2*2 allele leads to lower rates of alcohol use and problems, but thus far support for this pathway only exists from cross-sectional and laboratory data. The current study proposes to test this hypothesized pathway using ecologically valid assessment of real-time drinking behavior of individuals who possess one ALDH2*2 allele compared with those who possess no ALDH2*2 alleles. Participants will be a subset of 36 Asian American individuals who have participated in a previous study and thus are already well characterized in terms of genotypes, alcohol phenotypes, and other related variables. Each participant will be assessed in a laboratory alcohol challenge to calibrate the TAS device and then will wear the device and use the iPhone and website to record responses to alcohol over the next 2 weeks. The data obtained will be used to show feasibility and to determine effect sizes of ALDH2*2 and the necessary sample size for a larger future study. In addition, substantive hypotheses on the effects of ALDH2*2 will be preliminarily tested in this pilot sample. It is hypothesized that individuals with an ALDH2*2 allele will drink to reach similar subjective levels of response to alcohol compared with those without this protective allele, but will have lower rates of consumption, BACs, and negative consequences. Study feasibility will be assessed using a number of objective (e.g., percent of assessments missed) and subjective (e.g., perceived effects of self- monitoring on behavior) measures. Multilevel models will be used to simultaneously estimate within-person (e.g., BACs, responses to alcohol) and between-person (e.g., ALDH2 genotype) data. These two- and three- level models will compare patterns of use, BACs, subjective responses, and negative consequences across genotypes to determine effect sizes. This study will improve our ability to measure real-time alcohol involvement and our understanding of how genetic variations affect drinking behavior, reactions to alcohol, and the development of alcohol-related problems. PUBLIC HEALTH RELEVANCE: This study will advance methodological techniques for collecting prospective, ecologically valid assessments of real-time drinking behavior. Through the application of these methodological advancements, the proposed research will enhance our understanding of how genetic variations affect drinking behavior, reactions to alcohol, and the development of alcohol-related problems.