Evaluation of the Influence of Alcohol Dehydrogenase Polymorphisms on Alcohol Elimination Rates in African Americans
Article first published online: 5 AUG 2013
Copyright © 2013 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 38, Issue 1, pages 51–59, January 2014
How to Cite
Marshall, V. J., Ramchandani, V. A., Kalu, N., Kwagyan, J., Scott, D. M., Ferguson, C. L. and Taylor, R. E. (2014), Evaluation of the Influence of Alcohol Dehydrogenase Polymorphisms on Alcohol Elimination Rates in African Americans. Alcoholism: Clinical and Experimental Research, 38: 51–59. doi: 10.1111/acer.12212
- Issue published online: 21 JAN 2014
- Article first published online: 5 AUG 2013
- Manuscript Accepted: 20 MAY 2013
- Manuscript Received: 25 SEP 2012
- National Institute of Alcohol Abuse and Alcoholism. Grant Numbers: AA-11898, AA-012553
- Howard University General Clinical Research Center. Grant Number: M01-RR10284
- Alcohol Dehydrogenase Polymorphisms;
- Breath Alcohol Clamping;
- Alcohol Elimination Rate;
- African Descent Population;
- Sib Pair Analysis
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.