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A novel polymorphism of the brain-derived neurotrophic factor (BDNF) gene associated with late-onset Alzheimer's disease

Molecular Psychiatry volume 6, pages 83–86 (2001)Cite this article

Abstract

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.

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Acknowledgements

This work was supported by the Pharmacopsychiatry Research Foundation. We thank Ms N Okuyama for her assistance in the laboratory.

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Authors and Affiliations

  1. Department of Psychiatry, Teikyo University School of Medicine, Tokyo, Japan

    H Kunugi & S Nanko

  2. Department of Neurology, Jichi Medical School, Omiya Medical Center, Omiya City, Japan

    A Ueki & M Otsuka

  3. Department of Psychiatry, Tokyo Metropolitan Toshima Hospital, Tokyo, Japan

    K Isse

  4. Department of Psychiatry, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan

    H Hirasawa

  5. Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan

    N Kato

  6. Department of Laboratory Medicine, Shimane Medical University, Shimane, Japan

    T Nabika

  7. Department of Internal Medicine, Shimane Medical University, Shimane, Japan

    S Kobayashi

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  1. H Kunugi
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Correspondence to H Kunugi.

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Kunugi, H., Ueki, A., Otsuka, M. et al. A novel polymorphism of the brain-derived neurotrophic factor (BDNF) gene associated with late-onset Alzheimer's disease. Mol Psychiatry 6, 83–86 (2001). https://doi.org/10.1038/sj.mp.4000792

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