title: Dynamin 2 gene is a novel susceptibility gene for late-onset Alzheimer disease in non-APOE-epsilon4 carriers.
abstract: Alzheimer disease (AD) is characterized by progressive cognitive decline caused by synaptic dysfunction and neurodegeneration in the brain, and late-onset AD (LOAD), genetically classified as a polygenetic disease, is the major form of dementia in the elderly. It has been shown that beta amyloid, deposited in the AD brain, interacts with dynamin 1 and that the dynamin 2 (DNM2) gene homologous to the dynamin 1 gene is encoded at chromosome 19p13.2 where a susceptibility locus has been detected by linkage analysis. To test the genetic association of LOAD with the DNM2 gene, we performed a case-control study of 429 patients with LOAD and 438 sex- and age-matched control subjects in a Japanese population. We found a significant association of LOAD with single nucleotide polymorphism markers of the DNM2 gene, especially in non-carriers of the apolipoprotein E-epsilon4 allele. Even though subjects with the genotype homozygous for the risk allele at rs892086 showed no mutation in exons of the DNM2 gene, expression of DNM2 mRNA in the hippocampus was decreased in the patients compared to non-demented controls. We propose that the DNM2 gene is a novel susceptibility gene for LOAD.
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
authors.forename: Nuripa Jenishbekovna
authors.initials: NJ
authors.lastname: Aidaralieva
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan. kkamino@psy.med.osaka-u.ac.jp.|Shoraiso National Hospital, Yamatokoriyama, Nara, Japan. kkamino@psy.med.osaka-u.ac.jp.
authors.forename: Kouzin
authors.initials: K
authors.lastname: Kamino
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Kimura
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Morihara
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kazui
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Hashimoto
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudo
authors.affiliation: Shoraiso National Hospital, Yamatokoriyama, Nara, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kida
authors.affiliation: Shoraiso National Hospital, Yamatokoriyama, Nara, Japan.
authors.forename: Jun-Ichiro
authors.initials: JI
authors.lastname: Okuda
authors.affiliation: Department of Psychiatry, Osaka General Medical Center, Osaka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Uema
authors.affiliation: Department of Preventive Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors.forename: Hidehisa
authors.initials: H
authors.lastname: Yamagata
authors.affiliation: Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miki
authors.affiliation: Choju Medical Institute, Fukushimura Hospital, Toyohashi, Aichi, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Akatsu
authors.affiliation: Choju Medical Institute, Fukushimura Hospital, Toyohashi, Aichi, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kosaka
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeda
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D034285:Dynamin II / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
chemical_list: D034285:Dynamin II