Lind Penelope A, Eriksson C J Peter, Wilhelmsen Kirk C
Department of Genetic Epidemiology, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, QLD 4029, Australia.
Hum Genomics. 2008 Sep;3(1):24-35. doi: 10.1186/1479-7364-3-1-24.
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.
肝脏胞质醛脱氢酶1（ALDH1A1）此前已被证实与酒精依赖和饮酒行为有关，并且在白种人中，它与酒精引起的脸红和酒精敏感性有关。本研究对从酒精中毒临床治疗机构招募的无关男性芬兰队列（n = 104）和普通人群（n = 201）中，检测ALDH1A1与饮酒行为以及问题饮酒或酒精依赖易感性之间的关联。所有参与者均完成酒精使用障碍识别测试（AUDIT），并对ALDH1A1内部或侧翼的八个单核苷酸多态性（SNP）进行基因分型。为了测试饮酒行为与这些多态性之间的关联，我们使用了广义线性模型和单倍型分析。三个SNP与评估饮酒行为的定量AUDIT评分存在名义上的关联（rs348449，p = 0.043；rs610529，p = 0.013；rs348479，p = 0.025）。两位点（rs610529 - rs2288087）单倍型分析增强了与AUDIT评分的关联强度（p = 0.0015）。此外，rs348449与问题饮酒高度相关（等位基因优势比[OR] 7.87，95％置信区间[CI] 1.67 - 37.01），但由于次要等位基因频率较低（对照组和问题饮酒者中分别为0.01和0.07），需要更多样本才能验证这一观察结果。相反，rs348479（p = 0.019）和rs610529（等位基因OR 0.65，95％CI 0.43 - 0.98；基因型OR 0.32，95％CI 0.12 - 0.84）与酒精依赖状态有关。本研究为ALDH1A1在我们芬兰人群的饮酒行为（包括问题饮酒以及可能的酒精依赖）中所起的作用提供了进一步证据。
