The role of aldehyde dehydrogenase-1 (ALDH1A1) polymorphisms in harmful alcohol consumption in a Finnish population.
- Authors
- Lind, Penelope A; Eriksson, C J Peter; Wilhelmsen, Kirk C
- Year
- 2008
- Journal
- Human genomics
- PMID
- 19129088
- DOI
- 10.1186/1479-7364-3-1-24
- PMCID
- PMC3525184
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 (rs610529-rs2288087) haplotype analysis increased the strength of association with AUDIT score ( p = 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 = 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.
A schematic representation of the human ALDH1A1 gene structure and linkage disequilibrium (LD). The gene structure of ALDH1A1 is shown with exons numbered and relative exon size denoted by the width of the vertical bars. The eight SNPs analysed in this study are shown in relation to their location across ALDH1A1 and regions of low to high pair-wise LD, as measured by the r2 statistic, are represented by light grey to black shading, respectively.
Plot of minus log of p-value for Qtphase single-point and sliding window haplotype analysis of association between eight ALDH1A1 SNPs and the AUDIT score, a quantitative measure of alcohol consumption behaviour.
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