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Background: Cytosolic aldehyde dehydrogenase (ALDH1A1) is an important enzyme in the metabolism of acetaldehyde and the synthesis of retinoic acid. Two polymorphisms in the promoter region of ALDH1A1-ALDH1A1*2 and ALDH1A1*3-have recently been identified and described in small samples of Asian, Caucasian, and African individuals. The aim of this study was to determine the prevalence of these polymorphisms in a sample of Southwest California Indians and to test for associations with alcohol dependence and other substance-related behaviors.

Methods: The participants in this study were 463 adult men and women recruited from 8 contiguous Indian reservations. A structured interview was used to gather information on demographics, psychiatric diagnoses, and personal drinking and drug use history. A blood sample was obtained from each participant, and leukocyte DNA was extracted and used to genotype for the presence of the ALDH1A1 promoter polymorphisms.

Results: Twenty-seven participants (6%) possessed ALDH1A1*2 (frequency, 0.03), two participants possessed ALDH1A1*3, and one participant displayed both of these alleles. Individuals with an ALDH1A1*2 allele had lower rates of alcohol dependence and regular tobacco use than those without this allele. Individuals with ALDH1A1*2 also reported a significantly lower maximum number of drinks ever consumed in a 24-hr period, reported drinking fewer drinks per occasion when they first started drinking regularly, and reported lower expectations of alcohol's effects compared with individuals without this allele.

Conclusions: Results from this study suggest that ALDH1A1*2 may be associated with protection from the development of alcohol and other substance use disorders.

(C)2004Research Society on Alcoholism