Dynamin 2 gene is a novel susceptibility gene for late-onset Alzheimer disease in non-APOE-epsilon4 carriers.
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.
Aidaralieva
Nuripa Jenishbekovna
NJ
Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
Kamino
Kouzin
K
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.
Kimura
Ryo
R
Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
Yamamoto
Mitsuko
M
Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
Morihara
Takeshi
T
Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
Kazui
Hiroaki
H
Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
Hashimoto
Ryota
R
Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
Tanaka
Toshihisa
T
Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
Kudo
Takashi
T
Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
Kida
Tomoyuki
T
Shoraiso National Hospital, Yamatokoriyama, Nara, Japan.
Okuda
Jun-Ichiro
JI
Shoraiso National Hospital, Yamatokoriyama, Nara, Japan.
Uema
Takeshi
T
Department of Psychiatry, Osaka General Medical Center, Osaka, Japan.
Yamagata
Hidehisa
H
Department of Preventive Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Miki
Tetsuro
T
Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Akatsu
Hiroyasu
H
Choju Medical Institute, Fukushimura Hospital, Toyohashi, Aichi, Japan.
Kosaka
Kenji
K
Choju Medical Institute, Fukushimura Hospital, Toyohashi, Aichi, Japan.
Takeda
Masatoshi
M
Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
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
D034285:Dynamin II