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 = 104) and from the general population (n = 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 = 0.043; rs610529, p = 0.013; rs348479, p = 0.025) with the quantitative AUDIT score, which evaluates alcohol consumption behaviour. Two-locus (rs6I0529-rs2288087) haplotype analysis increased the strength of association with AUDIT score (p = 0.00I5). 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 = 0.019) and rs6I0529 (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.
Highlights
Cystolic aldehyde dehydrogenase (ALDH1A1) has been associated with alcohol-induced flushing in Caucasians, and alcohol sensitivity and dependence,[1,2] and functions in the detoxification of acetaldehyde, the first metabolite of ethanol oxidation.[3]
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 1⁄4 104) and from the general population (n 1⁄4 201)
The majority of alcohol studies related to the aldehyde dehydrogenase family focus on ALDH2, in Asian populations,[25,26] recent studies[1,8,9] are shining light on the role that ALDH1A1 may play in several human alcohol-related traits
Summary
Cystolic aldehyde dehydrogenase (ALDH1A1) has been associated with alcohol-induced flushing in Caucasians, and alcohol sensitivity and dependence,[1,2] and functions in the detoxification of acetaldehyde, the first metabolite of ethanol oxidation.[3]. This role in the regulation of DA degradation may be important in the development and maintenance of excessive alcohol consumption because VTA DA function can be ethanol induced via increased DA neurone firing, and the VTA lies within the mesolimbic system, which functions in reward, motivation and various substance disorders, including alcohol dependence.[5,6]
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