Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Human Psychopharmacology Laboratory, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Int J Neuropsychopharmacol. 2024 Oct 1;27(10). doi: 10.1093/ijnp/pyae035.
Alcohol and nicotine interact with the nicotinic acetylcholine receptor system to alter reward-related responses, thereby contributing to the co-use and misuse of these drugs. A missense polymorphism rs16969968 (G>A) in the CHRNA5 gene has shown a strong association with nicotine-related phenotypes. However, less is known about the impact of this variant on alcohol-related phenotypes.
We assessed the main and interactive effect of smoking and rs16969968 polymorphism on alcohol consumption using the Alcohol Use Disorders Identification Test (AUDIT), Timeline Follow Back (TLFB), and Lifetime Drinking History (LDH) in 980 healthy adults without alcohol use disorder. We further examined the effect of the rs16969968 polymorphism on acute alcohol consumption using a free-access i.v. alcohol self-administration (IV-ASA) human laboratory paradigm in a subset of 153 nonsmoking participants. Subjective alcohol responses, alcohol sensitivity, and expectancy measures were compared between genotype groups (GG; AA/AG).
We observed a significant association of smoking with AUDIT, TLFB, and LDH measures across genotype groups, with smokers showing higher scores compared with nonsmokers. Additionally, we found an association between genotype and TLFB-total drinks in the IV-ASA subset, with the GG group showing higher scores than AA/AG group. Relatedly, the alcohol negative expectancy score was significantly lower in the GG group than the AA/AG group.
Our findings underscore the association of smoking with alcohol measures. We found preliminary evidence for the protective effect of the functional CHRNA5 polymorphism on alcohol consumption and its association with increased negative alcohol expectancies, which highlights the substantial heterogeneity in alcohol responses.
酒精和尼古丁与烟碱型乙酰胆碱受体系统相互作用，改变与奖励相关的反应，从而导致这些药物的共同使用和滥用。CHRNA5 基因中的错义多态性 rs16969968（G>A）与尼古丁相关表型有很强的关联。然而，关于该变体对酒精相关表型的影响知之甚少。
我们使用酒精使用障碍识别测试（AUDIT）、时间线回溯（TLFB）和终生饮酒史（LDH），在 980 名没有酒精使用障碍的健康成年人中，评估了吸烟和 rs16969968 多态性对酒精消费的主要和交互作用。我们进一步在 153 名不吸烟的参与者的亚组中使用无限制静脉内酒精自我给药（IV-ASA）人类实验室范式，检查了 rs16969968 多态性对急性酒精消费的影响。在基因型组（GG；AA/AG）之间比较了主观酒精反应、酒精敏感性和预期测量。
我们观察到吸烟与 AUDIT、TLFB 和 LDH 测量值在基因型组之间存在显著关联，与不吸烟者相比，吸烟者的得分更高。此外，我们在 IV-ASA 亚组中发现了基因型与 TLFB-总饮酒量之间的关联，与 AA/AG 组相比，GG 组的得分更高。相关地，GG 组的酒精负预期得分显著低于 AA/AG 组。
我们的研究结果强调了吸烟与酒精测量值之间的关联。我们发现了功能 CHRNA5 多态性对饮酒的保护作用及其与增加的负酒精预期相关的初步证据，这突出了酒精反应的显著异质性。
