title: Polymorphisms in the aldehyde dehydrogenase 2 and dopamine β hydroxylase genes are not associated with Alzheimer's disease.
abstract: 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. ALDH2*2 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. ALDH2*2 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.
authors.affiliation: Department of Psychiatry, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Komatsu
authors.forename: Nobuto
authors.initials: N
authors.lastname: Shibata
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohnuma
authors.forename: Bolati
authors.initials: B
authors.lastname: Kuerban
authors.forename: Katrin
authors.initials: K
authors.lastname: Tomson
authors.forename: Aiko
authors.initials: A
authors.lastname: Toda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tagata
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nakada
authors.forename: Hiromi
authors.initials: H
authors.lastname: Shimazaki
authors.forename: Heii
authors.initials: H
authors.lastname: Arai
mesh_terms: D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D004299:Dopamine beta-Hydroxylase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial