Howard University Alcohol Research Center , Washington, District of Columbia.
Alcohol Clin Exp Res. 2014 Jan;38(1):51-9. doi: 10.1111/acer.12212. Epub 2013 Aug 5.
The relationship between alcohol dehydrogenase (ADH) polymorphisms and alcohol use disorders in populations of African descent has not been clearly established. This study examined the effect of ADH1B polymorphisms on alcohol metabolism and subjective response, following intravenous (IV) alcohol administration, and the influence of gender, recent drinking history, and family history of alcoholism (FHA), in nondependent African American drinkers.
The sample included eighty-seven 21- to 35-year-old, light social drinkers of African descent. Participants included 39 sib pairs, 2 sibships with 3 siblings each, and 3 individuals who were not part of a sibship. Participants received infusions via the use of the clamp method that refers to the goal of controlling breath alcohol concentration in 2 randomized sessions at 0.06 g% ethanol and 0 mg% (placebo), and a battery of subjective scales at predefined time points. Dependent measures included alcohol elimination rates (AERs), alcohol disappearance rates (ADRs), subjective measures peak scores, and area under the curve. General linear model and mixed models were performed to examine the relationship between ADH1B genotype, dependent measures, and influence of covariates.
Participants with ADH1B1/1 genotypes showed higher number of drinks (p = 0.023) and drinks per drinking day (p = 0.009) compared with the persons with ADH1B1/3 genotype. AER (adjusted for body weight) was higher in ADH1B*1 homozygotes (p = 0.045) compared with ADH1B1/3 heterozygotes. ADR differed significantly between males and females (p = 0.002), regardless of body weight (p = 0.004) and lean body mass (p < 0.001) adjustments. Although a few subjective measures differed across genotype, all measures were higher in alcohol sessions compared with placebo sessions (p < 0.001). These observations were mediated by drinks per drinking day, gender, and FHA.
ADH1B polymorphism had a marginal effect on alcohol pharmacokinetics following IV alcohol administration in nondependent drinkers of African descent. Session (alcohol vs. placebo) and ADH1B genotype did, however, influence subjective response to alcohol with some variation by gender, FHA, and drinks per drinking day.
酒精脱氢酶（ADH）多态性与非洲裔人群的酒精使用障碍之间的关系尚未明确。本研究通过静脉（IV）给予酒精后检查 ADH1B 多态性对酒精代谢和主观反应的影响，以及性别、近期饮酒史和家族酗酒史（FHA）对非依赖的非洲裔美国饮酒者的影响。
样本包括 87 名 21 至 35 岁的轻度社交饮酒的非洲裔。参与者包括 39 对同卵双胞胎、2 个每个有 3 个兄弟姐妹的同卵双生子和 3 个不属于同卵双生子的个体。参与者在 2 个随机的输注过程中使用夹钳法接受输注，目标是控制呼吸中的酒精浓度在 2 个随机输注过程中达到 0.06 g%乙醇和 0 mg%（安慰剂），并在规定的时间点进行一系列主观量表评估。因变量包括酒精消除率（AER）、酒精消失率（ADR）、主观指标峰度和曲线下面积。采用一般线性模型和混合模型来检验 ADH1B 基因型与因变量之间的关系以及协变量的影响。
ADH1B1/1 基因型的参与者饮酒量（p = 0.023）和饮酒日饮酒量（p = 0.009）均高于 ADH1B1/3 基因型的参与者。ADH1B*1 纯合子的 AER（按体重校正）高于 ADH1B1/3 杂合子（p = 0.045）。ADR 在男性和女性之间存在显著差异（p = 0.002），而与体重（p = 0.004）和瘦体重（p < 0.001）调整无关。尽管一些主观指标在基因型之间存在差异，但与安慰剂期相比，所有指标在酒精期均升高（p < 0.001）。这些观察结果受饮酒量、性别和 FHA 的影响。
在非依赖的非洲裔饮酒者中，ADH1B 多态性对 IV 给予酒精后的酒精药代动力学有一定影响。然而，与安慰剂相比，酒精和 ADH1B 基因型会影响对酒精的主观反应，其受性别、FHA 和饮酒量的影响存在差异。
