Alcohol and HIV risk: Genetic and endophenotype approaches

酒精和艾滋病毒风险：遗传和内表型方法

• 批准号: 7942964
• 负责人: Christian S Hendershot
• 金额: $ 3.26万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-19 至 2011-04-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7942964
• 关键词: Accounting; Adolescence; Adolescent; Alcohol consumption; Alcohols; Alleles; Attention; Attention deficit hyperactivity disorder; Behavior; Behavioral; Behavioral Genetics; Biological; Biological Factors; Candidate Disease Gene; Characteristics; Cognitive; Conduct Disorder; Consumption; DRD4 gene; Decision Making; Disease; Disease susceptibility; Disinhibition; Drug usage; Equation; Event; Genes; Genetic; Genetic Polymorphism; Genetic Research; Genetic Risk; Goals; HIV; Impulsivity; Individual; Investigation; Joints; Knowledge; Link; Measures; Mental disorders; Methods; Minisatellite Repeats; Modeling; Neurobiology; Neurocognitive; Outcome; Patient Self-Report; Performance; Phenotype; Public Health; Reporting; Research; Rewards; Risk; Risk Behaviors; Risk-Taking; Role; Sex Behavior; Single Nucleotide Polymorphism; Symptoms; Testing; Theoretical model; Unsafe Sex; Variant; adjudicate; alcohol risk; analog; base; cofactor; cohort; discounting; drinking; endophenotype; externalizing behavior; genetic variant; high risk; indexing; mesolimbic system; prospective; response; sex; sex risk; social; theories; trait; transmission process; young adult

Alcohol use Is a significant behavioral cofactor for HIV transmission. The association of alcohol with sexual risk behavior appears especially strong among high-risk adolescents, including adjudicated adolescents, who are at particular risk due to high rates of alcohol use and comorbid psychiatric disorders. Theoretical models of sexual risk behavior rely almost exclusively on social-cognitive perspectives. Basic knowledge about biological influences on HIV risk behavior, including alcohol-related risk taking, is virtually non-existent. Externalizing behaviors in adolescence and young adulthood show a common genetic diathesis, suggesting common biological and/or temperamental influences. In particular, shared genetic risk for a spectrum of externalizing behaviors, including sexual behavior, is attributed to a highly heritable factor reflecting behavioral disinhibition. Recent research has linked specific genetic variants to cognitive, behavioral and neurobiological phenotypes associated with behavioral disinhibition and externalizing disorders. Given the importance of the mesolimbic dopamine system in reward-related behavior and risk-based decision-making, genes with implications for dopaminergic function are high-priority candidates. The goal of the proposed research is to evaluate genetic factors that may a) predict common risk for alcohol use, sexual risk behavior and other externalizing behaviors, and/or b) moderate the association of alcohol use and HIV risk behavior. This research will take place in the context of a prospective investigation of genetic and neurobiological correlates of alcohol and HIV risk-taking among adjudicated adolescents (R01AA017390-01). Analyses will examine genetic influences on alcohol use, HIV risk behaviors and externalizing behaviors using impulsivity/disinhibition as a plausible endophenotype. Specific hypotheses concerning the moderating effect of the DRD4 VNTR polymorphism on alcohol-related sexual risk behavior will be evaluated. This project, which responds to the need for integrative and translational methods in studies of alcohol and HiV risk, will contribute basic information about genetic factors and related behavioral characteristics that may place some individuals at elevated risk for HIV via the propensity for externalizing behaviors, including alcohol use.

饮酒是艾滋病毒传播的一个重要行为辅助因素。该协会的 酒精与性危险行为在高危青少年中尤其严重， 包括因酗酒和合并症而面临特殊风险的青少年 精神疾病。危险性行为的理论模型几乎依赖于 完全基于社会认知角度。有关艾滋病毒风险的生物学影响的基本知识 包括与酒精相关的冒险行为在内的行为几乎不存在。外化行为 青春期和青年期表现出共同的遗传素质，表明共同的生物学和/或 气质影响。特别是，一系列共同的遗传风险 外化行为，包括性行为，归因于高度遗传的因素，反映了 行为去抑制。最近的研究有 将特定的遗传变异与相关的认知、行为和神经生物学表型联系起来 行为去抑制和外化障碍。鉴于中脑边缘多巴胺系统在奖励相关中的重要性 行为和基于风险的决策，对多巴胺能功能有影响的基因是 高优先级候选人。拟议研究的目标是评估可能 a) 预测的遗传因素 饮酒、性危险行为和其他外化行为的常见风险，和/或 b) 缓和 饮酒与艾滋病毒危险行为之间的关联。这项研究将在以下背景下进行 酒精与艾滋病毒冒险行为的遗传和神经生物学相关性的前瞻性调查 已判决的青少年 (R01AA017390-01)。分析将检查遗传对饮酒、艾滋病毒的影响 使用冲动/去抑制作为合理的内表型的风险行为和外化行为。 关于 DRD4 VNTR 多态性对酒精相关性的调节作用的具体假设 将评估性危险行为。该项目满足了一体化和 酒精和艾滋病毒风险研究中的转化方法将提供基本信息 关于可能使某些人面临较高风险的遗传因素和相关行为特征 通过外化行为（包括饮酒）的倾向来预防艾滋病毒。

项目成果

Genetic testing for aldehyde dehydrogenase 2 deficiency in young adults.

年轻人乙醛脱氢酶 2 缺乏症的基因检测。

• DOI: 10.1038/tpj.2011.3
• 发表时间: 2011-08
• 期刊: The pharmacogenomics journal
• 作者: Hendershot CS