Association between BDNF G196A (Val66Met) polymorphism and cognitive impairment in patients with Parkinson's disease: a meta-analysis

Abstract

Brain-derived neurotrophic factor (BDNF) is widely expressed in the central nervous system and prolongs the survival of dopaminergic neurons in the substantia nigra. Several studies have recently investigated the association between BDNF G196A (Val66Met), a single nucleotide polymorphism influencing cognitive processes, and cognitive impairment in Parkinson's disease (PD), but with contradictory findings. Thus, this meta-analysis was performed to clarify the possible association. Relevant studies were identified by a systematic search of PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases. The strength of the association was evaluated using crude odds ratios and 95% confidence interval. Finally, six studies involving 532 cases and 802 controls were included. Our analyses suggested the G196A (Val66Met) polymorphism was significantly associated with cognitive impairment in PD, especially in Caucasian populations. In conclusion, BDNF G196A (Val66Met) is confirmed to be a risk factor for cognitive impairment in PD.

Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer

“…The BDNF Val66Met polymorphism has been associated with cerebral cortex plasticity [ 117 , 118 ], with gray matter structures [ 119 , 120 ], or white matter integrities and structural networks [ 121 , 122 ]. More specifically, BDNF Val66Met polymorphism is associated with cognitive processes [ 112 , 123 , 124 , 125 , 126 , 127 ], and cognitive impairment in neurodegenerative disease, such as Parkinson’s disease (PD) [ 128 , 129 ] and AD [ 130 , 131 ], and even more with several brain disorders, including MDD and bipolar disorder [ 132 , 133 , 134 , 135 , 136 , 137 ], epilepsy [ 138 , 139 , 140 ], schizophrenia [ 125 , 141 , 142 , 143 , 144 ], aging and dementia [ 145 ] and stroke [ 117 , 146 , 147 ]. Met66, but not Val66, BDNF pro-domain can induce the growth cone retraction in young hippocampal neurons [ 148 ].…”

Association between matrix metalloproteinase-1 (MMP-1) protein level and the risk of rheumatoid arthritis and osteoarthritis: a meta-analysis

“…We designed our analysis flowchart according to the guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) ( 13 ). Referring to the retrieval strategy of several published meta-analyses ( 14 – 16 ), two investigators performed the publication search for case-control studies from three databases, including Pubmed, Embase (Excerpta Medica Database), and WANFANG, until July 15, 2020. As an example, the search terms of Pubmed were: ((Arthritis, Rheumatoid) OR rheumatoid arthritis)) OR (Osteoarthritis) OR Osteoarthritides) OR Osteoarthrosis) OR Osteoarthroses) OR Arthritis, Degenerative) OR Arthritides, Degenerative) OR Degenerative Arthritides) OR Degenerative Arthritis) OR Osteoarthrosis Deformans)) AND (Matrix Metalloproteinase 1) OR Metalloproteinase 1, Matrix) OR Interstitial Collagenase) OR MMP1 Metalloproteinase) OR Metalloproteinase, MMP1) OR MMP-1 Metalloproteinase) OR MMP 1 Metalloproteinase) OR Metalloproteinase, MMP-1) OR Matrix Metalloproteinase-1) OR Pro-Matrix Metalloproteinase-1) OR Metalloproteinase-1, Pro-Matrix) OR Pro Matrix Metalloproteinase 1) OR Promatrixmetalloproteinase-1) OR Promatrixmetalloproteinase 1) OR proMMP-1) OR MMP1) OR MMP-1).…”

Association Between BDNF Val66Met Polymorphism and Mild Behavioral Impairment in Patients With Parkinson's Disease

“…Brain-derived neurotrophic factor (BDNF) is a crucial protein in the central nervous system (CNS) with a substantial role in differentiation, survival, and protection of CNS neurons (7). Studies have investigated a potential role for p.Val66Met (G758A, rs6265), a single-nucleotide polymorphism (SNP) in exon 11 of the BDNF gene, and PD (8)(9)(10). The p.Val66Met SNP substitutes a valine (Val) residue at position 66 with a methionine (Met) residue in the pro-domain of the BDNF protein (7).The Met allele has been found to be associated with cognitive impairments in PD patients and late-life psychiatric symptoms in the general population (8,9,11).…”

“…Studies have investigated a potential role for p.Val66Met (G758A, rs6265), a single-nucleotide polymorphism (SNP) in exon 11 of the BDNF gene, and PD ( 8 – 10 ). The p.Val66Met SNP substitutes a valine (Val) residue at position 66 with a methionine (Met) residue in the pro-domain of the BDNF protein ( 7 ).The Met allele has been found to be associated with cognitive impairments in PD patients and late-life psychiatric symptoms in the general population ( 8 , 9 , 11 ). This substitution is not transferred to the final form of BDNF; however, this structural change in the BDNF protein precursor can significantly decrease the secretion of BDNF extracellularly and subsequently reduce its availability to the CNS neurons ( 7 ).…”

“…Recent longitudinal data in Alzheimer disease (AD) patients revealed strong evidence of Met association with depression ( 15 ). Moreover, recent meta-analysis reported higher likelihood of mild cognitive impairment in PD patients with the Met allele ( 9 ). These evidences suggest a link between the p.Val66Met polymorphism and NPS in PD patients and therefore encourage an investigation of this relationship.…”