Cope Lora M, Munier Emily C, Trucco Elisa M, Hardee Jillian E, Burmeister Margit, Zucker Robert A, Heitzeg Mary M
University of Michigan, Department of Psychiatry, 4250 Plymouth Road, Ann Arbor, MI, 48109, USA; University of Michigan, Addiction Center, 4250 Plymouth Road, Ann Arbor, MI, 48109, USA.
University of Michigan, Department of Psychiatry, 4250 Plymouth Road, Ann Arbor, MI, 48109, USA; University of Michigan, Addiction Center, 4250 Plymouth Road, Ann Arbor, MI, 48109, USA; Florida International University, Department of Psychology, Center for Children and Families, 11200 SW 8th Street, Miami, FL, 33199, USA.
Alcohol. 2017 Mar;59:7-16. doi: 10.1016/j.alcohol.2016.12.001. Epub 2016 Dec 6.
The serotonin transporter-linked polymorphic region (5-HTTLPR) of the serotonin transporter gene (SLC6A4) has been previously associated with alcohol-related risk. Most findings point to short (S) allele carriers being at increased risk for negative alcohol outcomes relative to long allele homozygotes, although some work indicates a more complex relationship. The current prospective study aimed to clarify how and under what circumstances variations in 5-HTTLPR transmit risk for various alcohol-related outcomes. Participants were 218 adolescents and young adults (29% female) enrolled in the Michigan Longitudinal Study. We tested a moderated mediation model with 5-HTTLPR as the predictor, Self-Rating of the Effects of Alcohol (SRE) score as the mediator, alcohol-related outcomes as the dependent variables, parental monitoring as the moderator of the SRE to alcohol outcomes path, and prior drinks, sex, age, and body mass index as covariates. Four alcohol-related outcomes were tested. The S allele was associated with higher SRE scores (i.e., lower response to alcohol). Parental monitoring was a significant moderator: At low levels of parental monitoring, higher SRE scores predicted more drinks consumed and binge drinking episodes. At high levels of monitoring, higher SRE scores were significantly related to fewer alcohol-related problems. Findings suggest that one mechanism by which 5-HTTLPR variation transmits alcohol-related risk is through level of response to alcohol. Furthermore, the strength and direction of this effect varied by level of parental monitoring, indicating that even in the presence of genetic and physiological vulnerability, parents can influence the likelihood of offspring developing problematic alcohol-related behaviors.
血清素转运体基因（SLC6A4）的血清素转运体相关多态性区域（5-HTTLPR）先前已被证实与酒精相关风险有关。大多数研究结果表明，与长等位基因纯合子相比，短（S）等位基因携带者出现不良酒精后果的风险更高，尽管一些研究表明这种关系更为复杂。当前的前瞻性研究旨在阐明5-HTTLPR的变异如何以及在何种情况下传递各种酒精相关后果的风险。研究对象为218名参与密歇根纵向研究的青少年和青年成年人（29%为女性）。我们测试了一个调节中介模型，其中5-HTTLPR为预测变量，酒精效应自评（SRE）分数为中介变量，酒精相关后果为因变量，父母监督为SRE与酒精后果路径的调节变量，既往饮酒量、性别、年龄和体重指数为协变量。对四种酒精相关后果进行了测试。S等位基因与较高的SRE分数相关（即对酒精的反应较低）。父母监督是一个显著的调节变量：在父母监督水平较低时，较高的SRE分数预示着饮酒量增加和暴饮发作次数增多。在父母监督水平较高时，较高的SRE分数与较少的酒精相关问题显著相关。研究结果表明，5-HTTLPR变异传递酒精相关风险的一种机制是通过对酒精的反应水平。此外，这种效应的强度和方向因父母监督水平而异，这表明即使存在遗传和生理易感性，父母也可以影响后代出现有问题的酒精相关行为的可能性。
