Department of Psychology, University of Minnesota, 75 East River Road, Minneapolis, MN 55455, USA.
Alcohol Clin Exp Res. 2012 Nov;36(11):1882-91. doi: 10.1111/j.1530-0277.2012.01809.x. Epub 2012 May 7.
In the aldehyde dehydrogenase 2 (ALDH2) gene, the ALDH22 allele, prevalent in East Asian populations, encodes an enzyme with severely reduced activity, thereby disrupting the normal metabolism of alcohol. Possession of the ALDH22 allele has been repeatedly shown to be associated with lower risk for alcohol dependence and reduced alcohol use. However, relatively few studies have considered whether the magnitude of the effect of ALDH2 polymorphism upon drinking is related to developmental stage or varies by environmental context.
In a longitudinally assessed sample of 356 adopted adolescents and young adults of East Asian descent, we examined the progression over time of the relationship between ALDH2 genotype and multiple measures of drinking behavior. We also sought to determine whether the environmental influences of nonbiological parent and elder sibling alcohol use and misuse, as well as deviant peer behavior, moderated the effect of ALDH2 genotype upon alcohol use.
Across all measures of alcohol use, the association between ALDH22 allele possession and reduced drinking went from negligible to moderate between mid-adolescence and early adulthood. A combined index of adoptive parent alcohol use and misuse consistently moderated the protective effect of the ALDH22 allele across the measures of quantity and frequency of alcohol use, and symptomology, such that high parental alcohol use and misuse reduced the protective effect of the ALDH2*2 allele, while low parental alcohol use and misuse enhanced the effect of the allele. Neither a combined index of elder sibling alcohol use and misuse, nor deviant peer behavior was consistently related to the effect of ALDH2 genotype.
The protective effect of the ALDH2*2 allele increases over the course of adolescence and young adulthood and is modified by the environmental influence of parental alcohol use and misuse. As such, ALDH2 provides a model system for exploring the nature of gene-environment interplay across development.
在乙醛脱氢酶 2（ALDH2）基因中，常见于东亚人群的 ALDH22 等位基因编码一种活性严重降低的酶，从而破坏了酒精的正常代谢。已有研究反复表明，携带 ALDH22 等位基因与较低的酒精依赖风险和较少的饮酒量相关。然而，相对较少的研究考虑到 ALDH2 多态性对饮酒的影响程度是否与发育阶段有关，或者是否因环境背景而异。
在一个由东亚裔被收养的青少年和年轻人组成的纵向评估样本中，我们研究了随着时间的推移，ALDH2 基因型与多种饮酒行为测量之间的关系的进展。我们还试图确定非生物父母和年长兄弟姐妹的酒精使用和滥用以及异常同伴行为的环境影响是否调节了 ALDH2 基因型对酒精使用的影响。
在所有饮酒行为的测量中，ALDH22 等位基因的携带与从中期青少年到早期成年饮酒量减少之间的关联从微不足道变为中度。收养父母的酒精使用和滥用的综合指数一致地调节了 ALDH22 等位基因对酒精使用的保护作用，跨越了酒精使用量和频率以及症状的测量，即高父母的酒精使用和滥用会降低 ALDH2*2 等位基因的保护作用，而低父母的酒精使用和滥用则增强了该等位基因的作用。年长兄弟姐妹的酒精使用和滥用的综合指数以及异常同伴行为与 ALDH2 基因型的影响并不一致。
ALDH2*2 等位基因的保护作用在青少年和成年早期的过程中增加，并受到父母酒精使用和滥用的环境影响的调节。因此，ALDH2 提供了一个探索基因-环境相互作用在整个发育过程中性质的模型系统。
