Real-Time Assessment of Alcohol Use Across ALDH2 Genotypes

描述（由申请人提供）：拟议研究的目的是建立一个实时酒精介入评估方案，使测试醛脱氢酶基因ALDH2的机制途径成为可能。两种技术先进的设备，一个手腕透皮酒精传感器（TAS）设备和一个可以通过iPhone访问的网站，将进一步开发和测试，作为自然饮酒的实时测量。为了提高本研究和未来研究的可行性，本研究将在方法学上取得两项进步：1)一个计算机程序，使用从实验室酒精测试中获得的有限数量的参数，从TAS数据中计算BACs； 2)一个编程灵活且易于修改的网站，允许使用该技术解决其他研究问题。这些研究工具将用于检查ALDH2基因与饮酒行为的关系。迄今为止，ALDH2是与酒精依赖关系最密切的基因。对于拥有ALDH2*2等位基因导致较低的酒精使用率和问题的过程，已经假设了一种机制途径，但到目前为止，这一途径仅存在于横断面和实验室数据中。目前的研究建议通过对携带一个ALDH2*2等位基因的个体与不携带ALDH2*2等位基因的个体进行实时饮酒行为的生态有效评估来验证这一假设途径。参与者将是36名亚裔美国人的一个子集，他们参加了之前的研究，因此已经在基因型、酒精表型和其他相关变量方面得到了很好的表征。每位参与者将在实验室酒精测试中进行评估，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。获得的数据将用于证明可行性，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，本先导样本将对ALDH2*2影响的实质性假设进行初步检验。据推测，与没有这种保护性等位基因的人相比，携带ALDH2*2等位基因的人饮酒达到相似的主观酒精反应水平，但饮酒率、BACs和负面后果更低。研究的可行性将使用一些客观的（例如，错过评估的百分比）和主观的（例如，自我监控对行为的感知影响）措施来评估。将使用多水平模型同时估计人体内（例如，BACs，对酒精的反应）和人之间（例如，ALDH2基因型）数据。这些二级和三级模型将比较不同基因型的使用模式、bac、主观反应和负面后果，以确定效应大小。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、对酒精的反应以及酒精相关问题发展的理解。

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.