Effect of Met66 allele of the BDNF rs6265 SNP on regional gray matter volumes in patients with multiple sclerosis: A voxel-based morphometry study

Ramasamy, Deepa P.; Ramanathan, Murali; Cox, Jennifer L.; Antulov, Ronald; Weinstock‐Guttman, Bianca; Bergsland, Niels; Benedict, Ralph H. B.; Dwyer, Michael G.; Minagar, Alireza; Zivadinov, Robert

doi:10.1016/j.pathophys.2010.04.006

Cited by 25 publications

(15 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the human BDNF gene, a single-nucleotide polymorphism (SNP) rs6265 leads to an amino acid change from valine (Val) to methionine (Met) in position 66 (Val66Met) [ 16 – 18 ]. In MS, this polymorphism has been correlated with cognitive performance and measures of brain atrophy, with ambiguous results [ 19 – 21 ]. Accumulating evidence suggests the involvement of DNA methylation in the regulation of BDNF expression and in the pathology of several neurological diseases [ 22 – 25 ].…”

Section: Introductionmentioning

confidence: 99%

BDNF rs6265 polymorphism methylation in Multiple Sclerosis: A possible marker of disease progression

et al. 2018

View full text Add to dashboard Cite

IntroductionBrain-Derived Neurotrophic Factor (BDNF) and its most common polymorphism Val66Met are known to have a role in Multiple Sclerosis (MS) pathogenesis. Evidence is accumulating that there is an involvement of DNA methylation in the regulation of BDNF expression. The aim of this study was to assess in blood samples of MS patients the correlation between the methylation status of the CpG site near BDNF-Val66Met polymorphism and the severity of the disease.MethodsWe recruited 209 MS patients that were genotyped for the BDNF Val66Met polymorphism. For each patient we quantitatively measured the methylation level of cytosine included in the exonic CpG site that can be created or abolished by the Val66Met BDNF polymorphism. Furthermore, we analyzed the clinical history of each patient and determined the time elapsed since the onset of the disease and an EDSS score of 6.0.ResultsThe genetic analysis identified 122 (58.4%) subjects carrying the Val/Val genotype, 81 (38.8%) with Val/Met genotype, and 6 (2.8%) carrying the Met/Met genotype. When the endpoint of an EDSS score of 6 was taken into account by means of a survival analysis, 52 failures (i.e., reaching an EDSS score of 6) were reported. When the sample was stratified according to the percentage of the BDNF methylation, subjects falling below the median (median methylation = 81%) were at higher risk of failure (IRD = 0.016; 95%CI = 0.0050–0.0279; p = 0.004).ConclusionsIn patients with a high disease progression the hypomethylation of the BDNF gene could increase the secretion of the protective neurotrophin, so epigenetic modifications could be the organism response to limit a brain functional reserve loss. Our study suggests that the percentage of methylation of the BDNF gene could be used as a prognostic factor for disease progression toward a high disability in MS patient.

show abstract

Section: Introductionmentioning

confidence: 99%

BDNF rs6265 polymorphism methylation in Multiple Sclerosis: A possible marker of disease progression

et al. 2018

View full text Add to dashboard Cite

show abstract

“…In MS, the polymorphism Val66Met was correlated with cognitive performance and measures of brain atrophy, with ambiguous results. Indeed, it has been reported that the Met66 allele confers protection against cerebral atrophy [49][50][51], whilst in another study a greater severity of brain atrophy in Met66 carriers was reported [52]. Moreover, the Met66 allele has been associated with an increased connectivity between the hippocampus and posterior cingulate cortex in MS patients, whilst the opposite effect was observed in normal subjects [53].…”

Section: Introductionmentioning

confidence: 94%

Depression in multiple sclerosis: effect of brain derived neurotrophic factor Val66Met polymorphism and disease perception

Santoro

Nociti

Fino

et al. 2016

Euro J of Neurology

View full text Add to dashboard Cite

show abstract

“…However, because of the lower frequency of the Met allele in Caucasians (20%) compared with Asians (40–50%) ( Petryshen et al 2010 ), effects of Met homozygosity have not been adequately demonstrated in previous studies with Caucasian cohorts. Recent studies have indicated that the Met allele is associated with positive effects on rGMV in healthy adults ( Liu et al 2014 ) and in patients with multiple sclerosis ( Ramasamy et al 2011 ), systemic lupus erythematosus ( Oroszi et al 2006 ), and major depression ( Gonul et al 2011 ). In addition, the Met allele was correlated with positive effects on IQ scores ( Tsai et al 2004 ; Vyas and Puri 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of theBDNFVal66Met Polymorphism on Gray Matter Volume in Typically Developing Children and Adolescents

Hashimoto¹,

Fukui²,

Takeuchi³

et al. 2016

Cereb. Cortex

View full text Add to dashboard Cite

The Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) is associated with psychiatric disorders and regional gray matter volume (rGMV) in adults. However, the relationship between BDNF and rGMV in children has not been clarified. In this 3-year cross-sectional/longitudinal (2 time points) study, we investigated the effects of BDNF genotypes on rGMV in 185 healthy Japanese children aged 5.7–18.4 using magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) analyses. We found that the volume of the right cuneus in Met homozygotes (Met/Met) was greater than in Val homozygotes (Val/Val) in both exams, and the left insula and left ventromedial prefrontal cortex volumes were greater in Val homozygotes versus Met homozygotes in Exam l. In addition, Met homozygous subjects exhibited higher processing speed in intelligence indices than Val homozygotes and Val/Met heterozygotes at both time points. Longitudinal analysis showed that the left temporoparietal junction volume of Val/Met heterozygotes increased more substantially over the 3-year study period than in Val homozygotes, and age-related changes were observed for the Val/Met genotype. Our findings suggest that the presence of 2 Met alleles may have a positive effect on rGMV at the developmental stages analyzed in this study.

show abstract

Effect of Met66 allele of the BDNF rs6265 SNP on regional gray matter volumes in patients with multiple sclerosis: A voxel-based morphometry study

Cited by 25 publications

References 57 publications

BDNF rs6265 polymorphism methylation in Multiple Sclerosis: A possible marker of disease progression

BDNF rs6265 polymorphism methylation in Multiple Sclerosis: A possible marker of disease progression

Depression in multiple sclerosis: effect of brain derived neurotrophic factor Val66Met polymorphism and disease perception

Effects of theBDNFVal66Met Polymorphism on Gray Matter Volume in Typically Developing Children and Adolescents

Contact Info

Product

Resources

About