title: Association between the catechol-O-methyltransferase polymorphism Val158Met and Alzheimer's disease in a Japanese population.
abstract: OBJECTIVE
  Catechol-O-methyltransferase (COMT) plays an important role in dopamine degradation, which is associated with the pathophysiology of Alzheimer's disease (AD) and alcoholism. A functional COMT polymorphism, Val158Met (rs4680 G > A), affects the onset of AD and is associated with alcohol dependence through dopamine receptor sensitivity in the prefrontal cortex.
  
  
  METHODS
  The aim of this case-control study (398 cases and 149 controls) was to investigate whether Val158Met polymorphism influences the onset of AD stratified according to alcohol consumption and apolipoprotein E (APOE) status. We also used single photon-emission computed tomography (SPECT) to analyse 26 patients with AD with the polymorphism.
  
  
  RESULTS
  As a function of APOE status, the genotypic frequencies of rs4680 in patients with AD did not differ from those in controls. We detected a significant association between high alcohol consumption in patients with AD (HAC-AD group) and the polymorphism in genotypic and allelic frequencies. Logistic regression analyses demonstrated that the presence of the APOE genotype with rs4680 increased the risk for HAC-AD synergistically. Hyperperfusion in the right sub-lobar insula of patients with the G/G genotype was found compared with that of patients with the G/A genotype. SPECT studies showed a relationship between the polymorphism and compensatory reactions for dysfunctions of dopaminergic neurotransmission in AD pathophysiology.
  
  
  CONCLUSIONS
  Although genetic association between the polymorphism and the onset of AD in a Japanese population were not observed, the polymorphism affected the risk for HAC-AD.
authors.affiliation: Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Nobuto
authors.initials: N
authors.lastname: Shibata
authors.affiliation: Department of Psychiatry, Jikei University School of Medicine, Tokyo, Japan.|Division of Molecular Genetics, Institute of DNA Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nagata
authors.affiliation: Department of Psychiatry, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Tagai
authors.affiliation: Department of Psychiatry, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Shunichiro
authors.initials: S
authors.lastname: Shinagawa
authors.affiliation: Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohnuma
authors.affiliation: Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Kawai
authors.affiliation: Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kasanuki
authors.affiliation: Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Shimazaki
authors.affiliation: Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Toda
authors.affiliation: Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tagata
authors.affiliation: Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nakada
authors.affiliation: Department of Psychiatry, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Division of Molecular Genetics, Institute of DNA Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Heii
authors.initials: H
authors.lastname: Arai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000235:genetics; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007564:Japan; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D001057:Apolipoproteins E; D002394:Catechol O-Methyltransferase
keywords: Alzheimer's disease; alcohol; apolipoprotein E; catechol-O-methyltransferase; polymorphism; single photon-emission computed tomography