A novel polymorphism of the brain-derived neurotrophic factor (BDNF) gene associated with late-onset Alzheimer's disease.
Several lines of evidence have suggested altered functions of the brain-derived neurotrophic factor (BDNF) in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD). In the search for polymorphisms in the 5'-flanking and 5'-noncoding regions of the BDNF gene, we found a novel nucleotide substitution (C270T) in the noncoding region. We performed an association study between this polymorphism and AD in a Japanese sample of 170 patients with sporadic AD (51 early-onset and 119 late-onset) and 498 controls. The frequency of individuals who carried the mutated type (T270) was significantly more common in patients with late-onset AD than in controls (P = 0.00004, odds ratio: 3.8, 95% CI 1.9-7.4). However, there was no significant difference in the genotype distribution between the patients with early-onset AD and the controls, although this might be due to the small sample size of the early-onset group. Our results suggest that the C270T polymorphism of the BDNF gene or other unknown polymorphisms, which are in linkage disequilibrium, give susceptibility to late-onset AD. We obtained no evidence for the possible interactions between the BDNF and apolipoprotein E (APOE) genes, suggesting that the possible effect of the BDNF gene on the development of late-onset AD might be independent of the APOE genotype.
Kunugi
H
H
Department of Psychiatry, Teikyo University School of Medicine, Tokyo, Japan. hkunugi@med.teikyo-u.ac.jp
Ueki
A
A
Otsuka
M
M
Isse
K
K
Hirasawa
H
H
Kato
N
N
Nabika
T
T
Kobayashi
S
S
Nanko
S
S
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018807:Polymorphism, Single-Stranded Conformational
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D019208:Brain-Derived Neurotrophic Factor; D017931:DNA Primers