Schuckit Marc A, Smith Tom L, Kalmijn Jelger, Danko George P
University of California San Diego, Department of Psychiatry (116A), VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161-2002, USA.
Alcohol Clin Exp Res. 2005 Nov;29(11):1921-7. doi: 10.1097/01.alc.0000187154.94681.65.
A low level of response (LR) to alcohol is one of several genetically-influenced phenotypes associated with an elevated risk for heavy drinking and alcoholism. While most studies support the influence of genes for this characteristic, no data to date have addressed how LR established from alcohol challenges performs in similarly aged subjects across generations.
Between 1978 and 1988, 18-to-25-year-old non-alcohol-dependent Caucasian male drinkers participated in the San Diego Prospective Study alcohol challenges. The paradigms included self-reports of feelings of "High" and "Intoxication," as well as alcohol-related changes in body sway. In recent years, 40 18-to-29-year-old offspring of 25 of these original probands were tested using a similar protocol.
Despite the passage of two decades between laboratory sessions across generations, for family history positive (FHP) subjects, significant positive correlations were observed for subjective feelings of intoxication and body sway after alcohol. Parent-offspring correlations were in the predicted direction for subjective feelings for family history negatives (FHNs), but were not significant. Across offspring, LR values were lower for FHPs overall, with significant differences at 60 or 90 min for five items.
The similarities in LR across generations, while not proving heritability, are consistent with prior reports regarding genetic influences in the LR to alcohol. The significant correlations across generations and over two decades support the reliability of the alcohol challenge results.
对酒精的低反应水平（LR）是与大量饮酒和酒精中毒风险升高相关的几种受基因影响的表型之一。虽然大多数研究支持基因对这一特征的影响，但迄今为止尚无数据探讨通过酒精激发试验确定的LR在不同代际的同龄受试者中的表现。
1978年至1988年期间，18至25岁非酒精依赖的白人男性饮酒者参与了圣地亚哥前瞻性研究中的酒精激发试验。试验范式包括对“兴奋”和“醉酒”感觉的自我报告，以及与酒精相关的身体摇摆变化。近年来，使用类似方案对这些最初的25名先证者中的40名18至29岁的后代进行了测试。
尽管两代人之间的实验室测试相隔了二十年，但对于家族史阳性（FHP）受试者，饮酒后主观醉酒感觉和身体摇摆之间观察到显著的正相关。对于家族史阴性（FHN）受试者，亲子相关性在主观感觉方面符合预测方向，但不显著。在所有后代中，FHP总体的LR值较低，五项指标在60或90分钟时有显著差异。
LR在不同代际中的相似性虽然不能证明遗传性，但与先前关于酒精LR受基因影响的报告一致。两代人之间以及二十年期间的显著相关性支持了酒精激发试验结果的可靠性。
