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Associations of Variations in Alcohol Dehydrogenase Genes With the Level of Response to Alcohol in Non-Asians

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  • This work was supported by the Veterans Affairs Research Service, by funds provided by the State of California for medical research on alcohol and substance abuse through the University of California, San Francisco and by NIAAA Grants R01AA005526, R01AA11257, U10AA008401, P50AA07611, K02AA00269, and T32AA013525.

Reprint requests: Marc A. Schuckit, MD, Department of Psychiatry, University of California, San Diego, 3350 La Jolla Village Drive, San Diego, CA 92161; Fax: 858-552-7424; E-mail: mschuckit@ucsd.edu

Abstract

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.

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