Department of Psychiatry, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
J Neural Transm (Vienna). 2014 Apr;121(4):427-32. doi: 10.1007/s00702-013-1112-z. Epub 2013 Nov 8.
Since ethanol and its metabolite, acetaldehyde, are directly neurotoxic, alcohol intake could affect the development of Alzheimer's disease (AD). Mitochondrial aldehyde dehydrogenase 2 (ALDH2) metabolizes acetaldehyde into acetate and also protects against oxidative stress, playing an important role in the development of AD. The activity of dopamine β hydroxylase (DBH) is reduced in the hippocampus and neocortex in the AD brain. DBH is also involved in the pathophysiology of alcoholism. The aim of this study was to investigate whether polymorphisms of both ALDH2 and DBH genes were associated with AD. ALDH22 and two functional single nucleotide polymorphisms (SNPs) of the DBH gene were analyzed using a case-control study design. Our case-control data set consisted of 201 AD patients and 130 age-matched controls. We also analyzed stratifying by alcohol consumption and apolipoprotein E (APOE) genotypes. There were no associations between the SNPs studied here and the onset of AD. No synergetic associations were found among the SNPs, APOE and the risk for AD. Although high alcohol consumption AD (HAC-AD) patients were analyzed in detail, the current three SNPs were not related with HAC-AD. ALDH22 and functional SNPs of the DBH gene did not modify the risk for AD. Since our data set was constructed only with AD in a Japanese population, further detailed genetic analyses with other ethnic groups would be needed.
由于乙醇及其代谢产物乙醛具有直接的神经毒性，饮酒可能会影响阿尔茨海默病（AD）的发展。线粒体乙醛脱氢酶 2（ALDH2）将乙醛代谢为乙酸盐，还能抵抗氧化应激，在 AD 的发展中起着重要作用。AD 大脑中海马和新皮质中的多巴胺β羟化酶（DBH）活性降低。DBH 还参与了酒精中毒的病理生理学。本研究旨在探讨 ALDH2 和 DBH 基因的多态性是否与 AD 相关。使用病例对照研究设计分析了 ALDH22 和 DBH 基因的两个功能性单核苷酸多态性（SNP）。我们的病例对照数据集包括 201 名 AD 患者和 130 名年龄匹配的对照。我们还按饮酒量和载脂蛋白 E（APOE）基因型进行了分层分析。在这里研究的 SNP 与 AD 的发病无关。SNP、APOE 与 AD 风险之间没有协同关联。尽管详细分析了高酒精摄入 AD（HAC-AD）患者，但目前的三个 SNP 与 HAC-AD 无关。ALDH22 和 DBH 基因的功能性 SNP 并未改变 AD 的风险。由于我们的数据集仅由日本人群中的 AD 组成，因此需要与其他种族进行进一步的详细遗传分析。
