title: Association of aldehyde dehydrogenase-2 polymorphism with alcoholic polyneuropathy in humans.
abstract: Persons who have the Glu-487-->Lys mutation (single nucleotide polymorphism) of the aldehyde dehydrogenase-2 (ALDH2) gene have less ability to metabolize the alcohol breakdown product acetaldehyde. In order to clarify whether acetaldehyde is associated with the pathogenesis of alcoholic polyneuropathy, we compared nerve conduction data as well as clinical signs and symptoms of neuropathy between alcoholics with ALDH2*2 (Lys-487) heterozygotes and those with ALDH2*1 (Glu-487) homozygotes. Alcoholics with ALDH2*2 heterozygotes showed significantly lower sensory nerve action potential amplitudes of the sural and median nerves than those with ALDH2*1 homozygotes, suggesting that the accumulation of acetaldehyde due to ALDH2 inactivity is associated with alcoholic polyneuropathy.
authors.affiliation: Department of Neurology, National Institute on Alcoholism, Kurihama National Hospital, 5-3-1 Nobi, Yokosuka, Kanagawa 239-0841, Japan. masakit@mail.rockefeller.edu
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Masaki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Mochizuki
authors.forename: Sachio
authors.initials: S
authors.lastname: Matsushita
authors.forename: Akira
authors.initials: A
authors.lastname: Yokoyama
authors.forename: Keiko
authors.initials: K
authors.lastname: Kamakura
authors.forename: Susumu
authors.initials: S
authors.lastname: Higuchi
mesh_terms: D000200:Action Potentials / Q000502:physiology; D020269:Alcoholic Neuropathy / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D008239:Lysine / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction / Q000235:genetics / Q000502:physiology; D010525:Peripheral Nerves / Q000503:physiopathology; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: D012333:RNA, Messenger; D018698:Glutamic Acid; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D008239:Lysine