Associations of variations in alcohol dehydrogenase genes with the level of response to alcohol in non-Asians.
BACKGROUND
Risk and protective factors for alcohol use disorders (AUDs) are complex and reflect both environmental and genetic factors. Genetic components account for about 50% of the variation and influence several phenotypes, including the level of response (LR) to alcohol as well as alcohol-metabolizing enzyme polymorphisms. Variations in the ADH1B and ADH1C genes may influence the LR to alcohol by increasing levels of acetaldehyde during alcohol metabolism, although most data on this question come from Asian populations.


METHODS
This study evaluated associations of ADH1B and ADH1C genotypes in a non-Asian sample. Participants (N = 117, 69.2% female) were 18- to 29-year-old men and women, primarily Caucasian (70.1%) and black (26.5%), recruited in San Diego, California. The Semi-Structured Assessment for the Genetics of Alcoholism Interview was used to assess demographic, substance use, and psychiatric history information, and the Family History Assessment Module was used to determine first-degree family history of alcohol dependence. An alcohol challenge paradigm was used to gather data on the LR to alcohol over 210 minutes.


RESULTS
Participants with the ADH1B*1/*2 genotype had a higher LR to alcohol early in the alcohol challenge (i.e., 30, 60, and 90 minutes after drinking) as measured by both alcohol-related changes in subjective feelings of intoxication and body sway, even when controlling for sex and Russian/Eastern European ancestry. A similar trend was seen for ADH1C*1/*1 genotype, although the results were not significant.


CONCLUSIONS
These findings suggest that studies searching for genes relating to the LR to alcohol as a vulnerability factor for AUDs should consider controlling for ADH1B genotype, as the ADH1B*2 allele could obscure the impact of other genetic polymorphisms.
Duranceaux
Nicole C E
NC
Department of Psychiatry, University of California, San Diego, California 92161, USA.
Schuckit
Marc A
MA
Eng
Mimy Y
MY
Robinson
Shannon K
SK
Carr
Lucinda G
LG
Wall
Tamara L
TL
D000293:Adolescent; D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D000437:Alcoholism / Q000235:genetics; D000483:Alleles; D044383:Black People; D002140:California / Q000453:epidemiology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D004856:Postural Balance / Q000187:drug effects; D044465:White People; D001741:Black or African American
D002492:Central Nervous System Depressants; D000431:Ethanol; C489332:ADH1B protein, human; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase