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Aging and disease    2018, Vol. 9 Issue (3) : 523-536     DOI: 10.14336/AD.2017.0717
Review Article |
BDNF Polymorphism: A Review of Its Diagnostic and Clinical Relevance in Neurodegenerative Disorders
Shen Ting1,*, You Yuyi2, Joseph Chitra1, Mirzaei Mehdi3, Klistorner Alexander1,2, Graham Stuart L.1,2, Gupta Vivek1
1Faculty of Medicine and Health Sciences, Macquarie University, Australia
2Save Sight Institute, Sydney University, Sydney, Australia
3Faculty of Science and Engineering, Macquarie University, Australia
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Brain-derived neurotrophic factor (BDNF) has a unique role in the neuronal development, differentiation, and survival in the developing and adult nervous system. A common single-nucleotide polymorphism in the pro-region of the human BDNF gene, resulting in a valine to methionine substitution (Val66Met), has been associated with the susceptibility, incidence, and clinical features of several neurodegenerative disorders. Much research has been dedicated to evaluating the effects of polymorphism in the past decade, and functional effects of this genetic variation. A better understanding of how this naturally occurring polymorphism associates with or influences physiology, anatomy, and cognition in both healthy and diseased adults in neurodegenerative conditions will help understand neurochemical mechanisms and definable clinical outcomes in humans. Here we review the role and relevance of the BDNF Val66Met polymorphism in neurodegenerative diseases, with particular emphasis on glaucoma, multiple sclerosis (MS), Alzheimer’s disease (AD) and Parkinson’s disease (PD). Several controversies and unresolved issues, including small effect sizes, possible ethnicity, gender, and age effects of the BDNF Val66Met are also discussed with respect to future research.

Keywords BDNF      polymorphism      neurodegenerative diseases      glaucoma      multiple sclerosis      Alzheimer’s disease     
Corresponding Authors: Shen Ting (current email address:   
About author: These authors have contributed equally to this work.
Issue Date: 05 June 2018
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Shen Ting
You Yuyi
Joseph Chitra
Mirzaei Mehdi
Klistorner Alexander
Graham Stuart L.
Gupta Vivek
Cite this article:   
Shen Ting,You Yuyi,Joseph Chitra, et al. BDNF Polymorphism: A Review of Its Diagnostic and Clinical Relevance in Neurodegenerative Disorders[J]. Aging and disease, 2018, 9(3): 523-536.
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EthnicityCohortTotal NReferenceAllele frequencyGenotype
A (Met) %G (Val) %A/A (Met/Met) %G/A (Val/Met) %G/G (Val/Val) %
AsianKorea244Pivac et al. 200946.353.723.445.930.7
Japan657Fukumoto et al. 200939.
Japan275Nishimura et al. 200942.557.517.150.932.0
China239Bian et al. 200545.454.621.348.130.5
Japan471Matsushita et al. 200544.555.520.847.431.9
Japan151Itoh et al. 200341.158.915.950.333.8
CaucasianRomania1124Vulturar et al. 201619.380.74.030.565.5
Poland193Nowak et al. 201415.
Croatia556Pivac et al. 200919.580.53.432.464.2
Italy233Guerini et al. 200920.679.44.332.663.1
Italy37Liguori et al. 200917.682.42.729.767.6
USA250Zhang et al. 200618.881.24.029.666.4
Finland920Vepsalainen et al. 200513.
USA194Bodner et al. 200519.
USA392Parsian et al. 200428.
Spain218Combarros et al. 200419.081.03.730.765.6
USA133Egan et al. 200318.082.04.527.168.4
Italy111Ventriglia et al. 200129.770.
Table 1  Allele and genotype distributions for the Val66Met polymorphism of Brain-derived neurotrophic factor (BDNF) in healthy subjects in different ethnicity.
Figure 1.  Changes in Brain-derived neurotrophic factor (BDNF) protein levels and BDNF Val66Met polymorphism as modifiers of neurodegenerative disorders and psychiatric disorders.
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