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Evaluation of the Influence of Alcohol Dehydrogenase Polymorphisms on Alcohol Elimination Rates in A frican A mericans
Author(s) -
Marshall Vanessa J.,
Ramchandani Vijay A.,
Kalu Nnenna,
Kwagyan John,
Scott Denise M.,
Ferguson Clifford L.,
Taylor Robert E.
Publication year - 2014
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12212
Subject(s) - adh1b , alcohol , alcohol dehydrogenase , medicine , placebo , demography , body mass index , ethanol , african descent , biology , biochemistry , dehydrogenase , branched chain alpha keto acid dehydrogenase complex , pathology , sociology , anthropology , enzyme , alternative medicine
The relationship between alcohol dehydrogenase ( ADH ) polymorphisms and alcohol use disorders in populations of A frican descent has not been clearly established. This study examined the effect of ADH 1 B 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 A frican A merican drinkers. Materials The sample included eighty‐seven 21‐ to 35‐year‐old, light social drinkers of A frican 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 ( AER s), alcohol disappearance rates ( ADR s), subjective measures peak scores, and area under the curve. General linear model and mixed models were performed to examine the relationship between ADH 1 B genotype, dependent measures, and influence of covariates. Results Participants with ADH 1 B 1/1 genotypes showed higher number of drinks ( p = 0.023) and drinks per drinking day ( p = 0.009) compared with the persons with ADH 1 B 1/3 genotype. AER (adjusted for body weight) was higher in ADH 1 B *1 homozygotes ( p = 0.045) compared with ADH 1 B 1/3 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 . Conclusions ADH 1 B polymorphism had a marginal effect on alcohol pharmacokinetics following IV alcohol administration in nondependent drinkers of A frican descent. Session (alcohol vs. placebo) and ADH 1 B genotype did, however, influence subjective response to alcohol with some variation by gender, FHA , and drinks per drinking day.