The role of aldehyde dehydrogenase-1 ( ALDH1A1 ) polymorphisms in harmful alcohol consumption in a Finnish population
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The role of aldehyde dehydrogenase-1 (ALDH1A1) polymorphisms in harmful alcohol consumption in a Finnish population Penelope A. Lind,1 C.J. Peter Eriksson2* and Kirk C. Wilhelmsen3 1
Department of Genetic Epidemiology, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, QLD 4029, Australia 2 Department of Mental Health and Alcohol Research, National Public Health Institute, P.O. Box 33, 00251 Helsinki, Finland 3 Department of Genetics and Neurology, Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, NC 27599, USA *Correspondence to: Tel: þ358 9 4744 8114; Fax: þ358 9 4744 8133; E-mail: [email protected] Date received (in revised form): 16th May, 2008
Abstract Liver cystolic aldehyde dehydrogenase 1 (ALDH1A1) has been previously associated with both alcohol dependence and alcohol consumption behaviour, and has been implicated in alcohol-induced flushing and alcohol sensitivity in Caucasians. The present study tested for association between ALDH1A1 and alcohol consumption behaviour and susceptibility to problem drinking or alcohol dependence in Finnish cohorts of unrelated male subjects recruited from alcoholism clinical treatment facilities (n ¼ 104) and from the general population (n ¼ 201). All participants completed the Alcohol Use Disorder Identification Test (AUDIT) and were genotyped for eight single nucleotide polymorphisms (SNPs) within or flanking ALDH1A1. To test for association between alcohol consumption behaviour and these polymorphisms, we used generalised linear models and haplotypic analysis. Three SNPs were nominally associated (rs348449, p ¼ 0.043; rs610529, p ¼ 0.013; rs348479, p ¼ 0.025) with the quantitative AUDIT score, which evaluates alcohol consumption behaviour. Two-locus (rs610529-rs2288087) haplotype analysis increased the strength of association with AUDIT score ( p ¼ 0.0015). Additionally, rs348449 is highly associated with problem drinking (allelic odds ratio [OR] 7.87, 95 per cent confidence interval [CI] 1.67 –37.01) but due to the low minor allele frequency (0.01 and 0.07 in controls and problem drinkers, respectively), more samples are required to validate this observation. Conversely, rs348479 ( p ¼ 0.019) and rs610529 (allelic OR 0.65, 95 per cent CI 0.43– 0.98; genotypic OR 0.32, 95 per cent CI 0.12 –0.84) are implicated in alcohol dependence status. This study provides further evidence for a role for ALDH1A1 in alcohol consumption behaviour, including problem drinking and possibly alcohol dependence, in our Finnish population. Keywords: acetaldehyde, ALDH1A1, alcohol use, alcohol abuse, alcohol dependence, association, single nucleotide polymorphism
Introduction Cystolic aldehyde dehydrogenase (ALDH1A1) has been associated with alcohol-induced flushing in Caucasians, and alcohol sensitivity and
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dependence,1,2 and functions in the detoxification of acetaldehyde, the first metabolite of ethanol oxidation.3 Additionally, ALDH1A1 is involved in the degradation of dopamine (DA) in the ventral
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