Real-Time Assessment of Alcohol Use Across ALDH2 Genotypes

实时评估 ALDH2 基因型的饮酒情况

• 批准号: 7809673
• 负责人: SUSAN E LUCZAK
• 金额: $ 17.85万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-20 至 2012-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7809673
• 关键词: Address; Affect; Alcohol Phenotype; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohols; Alleles; Asian Americans; Behavior; Blood alcohol level measurement; Calibration; Consumption; Data; Development; Devices; Electronic Mail; Electronics; Feasibility Studies; Future; Genes; Genetic Variation; Genotype; Individual; Ingestion; Internet; Laboratories; Limb structure; Location; Measurement; Measures; Methods; Modeling; Monitor; Participant; Pathway interactions; Pattern; Persons; Process; Protocols documentation; Reaction; Records; Relative (related person); Research; Sample Size; Sampling; Services; Skin; Staging; Techniques; Technology; Telephone; Testing; Time; Validity and Reliability; Wireless Technology; Wrist; alcohol behavior; alcohol involvement; alcohol measurement; alcohol related problem; alcohol research; alcohol response; aldehyde dehydrogenases; base; computerized; design; drinking; drinking behavior; flexibility; genetic variant; improved; mathematical model; multilevel analysis; new technology; programs; prospective; psychosocial; public health relevance; response; sensor; tool; web site

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.

描述（由申请人提供）：拟议研究的目的是建立实时酒精参与评估方案，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，即手腕透皮酒精传感器 (TAS) 设备和可通过 iPhone 访问的网站，将作为自然饮酒的实时测量进行进一步开发和测试。本研究将在方法上取得两项进展，以提高本研究和未来研究的可行性：1）一个计算机化程序，使用从实验室酒精测试中获得的有限数量的参数，根据 TAS 数据计算 BAC；2）一个网站编程灵活且易于修改，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联。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 等位基因会导致较低的饮酒率和问题的过程，人们假设存在一条机制途径，但迄今为止，仅从横截面数据和实验室数据中得出对这一途径的支持。目前的研究建议通过对具有 ALDH2*2 等位基因的个体与不具有 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，他们曾参加过之前的一项研究，因此在基因型、酒精表型和其他相关变量方面已经有了很好的特征。每位参与者都将在实验室酒精挑战中接受评估，以校准 TAS 设备，然后在接下来的两周内佩戴该设备并使用 iPhone 和网站记录对酒精的反应。获得的数据将用于展示可行性并确定 ALDH2*2 的效应大小以及未来更大规模研究所需的样本量。此外，有关 ALDH2*2 影响的实质性假设将在该试点样品中进行初步测试。据推测，与没有这种保护性等位基因的人相比，具有 ALDH2*2 等位基因的个体饮酒后对酒精的主观反应水平相似，但饮酒率、BAC 和负面后果较低。研究可行性将使用许多客观（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影响）措施进行评估。多级模型将用于同时估计人内（例如 BAC、酒精反应）和人间（例如 ALDH2 基因型）数据。这些两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实时测量酒精参与程度的能力，并提高我们对遗传变异如何影响饮酒行为、酒精反应以及酒精相关问题发展的理解。 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、生态有效评估的方法技术。通过应用这些方法论的进步，拟议的研究将增强我们对遗传变异如何影响饮酒行为、酒精反应以及酒精相关问题的发展的理解。

项目成果

A multimodal investigation of contextual effects on alcohol's emotional rewards.

• DOI: 10.1037/abn0000346
• 发表时间: 2018-05
• 期刊: Journal of abnormal psychology
• 影响因子: 4.6
• 作者: Fairbairn CE;Bresin K;Kang D;Rosen IG;Ariss T;Luczak SE;Barnett NP;Eckland NS
• 通讯作者: Eckland NS