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Aging and disease    2020, Vol. 11 Issue (6) : 1513-1526     DOI: 10.14336/AD.2020.0310
Review Article |
Influence of BDNF Genetic Polymorphisms in the Pathophysiology of Aging-related Diseases
Rodrigo Urbina-Varela1, María Inés Soto-Espinoza2, Romina Vargas1, Luis Quiñones3, Andrea del Campo1,*
1Laboratorio de Fisiología y Bioenergética Celular, Departamento de Farmacia, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Santiago, Chile.
2Escuela de Tecnología Médica, Facultad de Salud, Universidad Santo Tomás, Chile.
3Laboratorio de Carcinogenesis Química y Farmacogenética (CQF), Departamento de Oncología Básico-Clínica, Facultad de Medicina, Universidad de Chile.
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Abstract  

For the first time in history, most of the population has a life expectancy equal or greater than 60 years. By the year 2050, it is expected that the world population in that age range will reach 2000 million, an increase of 900 million with respect to 2015, which poses new challenges for health systems. In this way, it is relevant to analyze the most common diseases associated with the aging process, namely Alzheimer´s disease, Parkinson Disease and Type II Diabetes, some of which may have a common genetic component that can be detected before manifesting, in order to delay their progress. Genetic inheritance and epigenetics are factors that could be linked in the development of these pathologies. Some researchers indicate that the BDNF gene is a common factor of these diseases, and apparently some of its polymorphisms favor the progression of them. In this regard, alterations in the level of BDNF expression and secretion, due to polymorphisms, could be linked to the development and/or progression of neurodegenerative and metabolic disorders. In this review we will deepen on the different polymorphisms in the BDNF gene and their possible association with age-related pathologies, to open the possibilities of potential therapeutic targets.

Keywords Aging      BDNF gene      polymorphism      aging-related diseases     
Corresponding Authors: del Campo Andrea   
About author:

These authors contrinuted equally to this work.

Just Accepted Date: 01 May 2020   Issue Date: 19 November 2020
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Urbina-Varela Rodrigo
Soto-Espinoza María Inés
Vargas Romina
Quiñones Luis
del Campo Andrea
Cite this article:   
Urbina-Varela Rodrigo,Soto-Espinoza María Inés,Vargas Romina, et al. Influence of BDNF Genetic Polymorphisms in the Pathophysiology of Aging-related Diseases[J]. Aging and disease, 2020, 11(6): 1513-1526.
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http://www.aginganddisease.org/EN/10.14336/AD.2020.0310     OR
Figure 1.  Intracellular and extracellular modifications of BDNF. Intracellular cleavage eliminates the pre-region sequence (green box), this modification results in the formation of the immature pro-neurotrophin isoform of BDNF (yellow+blue). Furin eliminates the pro domain sequence and generates the mature isoform of BDNF (blue). The intracellular division that leads to the formation of m-BDNF can also occur in the intracellular vesicles. The processing of BDNF is carried out by intracellular proteases, regulated convertases, and Furin. As a result, both isoforms pro-BDNF and m-BDNF are released into the extracellular space. In the extracellular route, the pro-BDNF released in the extracellular space is processed by metalloproteinases 2 and 9 (MMP2 and MMP9) and Plasmin. Pro-BDNF can act over Sortilin and p75NTR receptors, while the prodomain acts over Sortilin and m-BDNF exerts its functions through the activation of TrkB receptors.
Table 1  shows a list of the most relevant SNPs on the BDNF gene that have been correlated with diseases, mostly focus on those correlating with the aging process.
SNPsPosition in ChromosomeNucleotide
Change
Protein effectRelated diseases
rs1076766427.704.439
T/A

Intron variant
Asthma [6]
Allergic Rhinitis [73] Obesity [67]
rs1083521027.654.363C/A/GIntron variantSchizophrenia [105]
rs1103010027.656.039C/T3'UTR variantAsthma [104]
rs1103010127.659.197
A/T

5'UTR variant
Depression
Asthma [104] Bipolar disorder [74]
rs1103010327.660.786A/GIntron variantDepression and Suicide [59]
rs1103010427.662.970A/GIntron variantPanic attacks
Bipolar disorder Alzheimer disease [50]
rs1103010727.673.288A/GIntron variantBipolar Disorder [83]
rs1227336327.723.312T/CIntron variantMajor Depressive Disorder[46] Bipolar disorder
rs1227353927.661.764C/TIntron variantDepression and suicide
rs1229106327.672.554T/CIntron variantObesity [16]
rs1330622127.701.142C/TIntron variantAlcohol dependency [100]
Heroin dependency [52]
rs1691723727.680.836G/TIntron variantBipolar Disorder [102]
Asthma
rs203032327.706.992A/CIntron variantObesity [35] [36]
rs203032427.705.368A/GIntron variantAlzheimer Disease [26]
Parkinson Disease [95] PTSD [41]
rs204904527.672.694G/A/CIntron variantBipolar Disorder
rs204904627.702.228T/AIntron variantObsesive Compulsive disorder
rs2872215127.659.629C/G5´ UTRDepression and suicide
rs4128291827.657.233A/C3´ UTRDepression and suicide
rs626527.658.369G/A
Missense variant G196A Val 66 Met
Major Depressive disorder
Hypertension AD PD T2D Depression Asthma Allergic Rhinitis
rs710341127.678.578C/TIntron variantPTSD
Epilepsy [41]
rs710387327.678.770G/A/CIntron variantDepression [65]
rs712750727.693.337T/CIntron variantHippocampal Volume in cerebral injury [44]
rs819246627.658.560G/A/TMissense variant
Thr2 Ile
Schizophrenia
rs96236927.712.873T/CIntron variantDepression and suicide [72]
rs98874827.703.198C/GIntron variantDepressive disorder
Bipolar disorder [88]
Table 1  BDNF polymorphisms and their relationship with multiple diseases. Each polymorphism was looked up in SNPedia and verified in the reference.
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