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Post-mortem multiple sclerosis lesion pathology is influenced by single nucleotide polymorphisms
- Source :
- Brain Pathology, 30, 106-119. Wiley-Blackwell, Fransen, N L, Crusius, J B A, Smolders, J, Mizee, M R, van Eden, C G, Luchetti, S, Remmerswaal, E B M, Hamann, J, Mason, M R J & Huitinga, I 2020, ' Post-mortem multiple sclerosis lesion pathology is influenced by single nucleotide polymorphisms ', Brain Pathology, vol. 30, no. 1, pp. 106-119 . https://doi.org/10.1111/bpa.12760, Brain Pathology (Zurich, Switzerland), Brain Pathology, 30(1), 106-119. Wiley-Blackwell, Brain pathology (Zurich, Switzerland), 30(1), 106-119. Wiley-Blackwell
- Publication Year :
- 2020
-
Abstract
- Over the last few decades several common single nucleotide polymorphisms (SNPs) have been identified that correlate with clinical outcome in multiple sclerosis (MS), but the pathogenic mechanisms underlying the clinical effects of these SNPs are unknown. This is in part due to the difficulty in the functional translation of genotype into disease-relevant mechanisms. Building on our recent work showing the association of clinical disease course with post-mortem MS lesion characteristics, we hypothesized that SNPs that correlate with clinical disease course would also correlate with specific MS lesion characteristics in autopsy tissue. To test this hypothesis 179 MS brain donors from the Netherlands Brain Bank MS autopsy cohort were genotyped for 102 SNPs, selected based on their reported associations with clinical outcome or their associations with genes that show differential gene expression in MS lesions. Three SNPs linked to MS clinical severity showed a significant association between the genotype and either the proportion of active lesions (rs2234978/FAS and rs11957313/KCNIP1) or the proportion of mixed active/inactive lesions (rs8056098/CLEC16A). Three SNPs linked to MS pathology-associated genes showed a significant association with either proportion of active lesions (rs3130253/MOG), incidence of cortical grey matter lesions (rs1064395/NCAN) or the proportion of remyelinated lesions (rs5742909/CTLA4). In addition, rs2234978/FAS T-allele carriers showed increased FAS gene expression levels in perivascular T cells and perilesional oligodendrocytes, cell types that have been implicated in MS lesion formation. Thus, by combining pathological characterization of MS brain autopsy tissue with genetics, we now start to translate genotypes linked to clinical outcomes in MS into mechanisms involved in MS lesion pathogenesis. This article is protected by copyright. All rights reserved.
- Subjects :
- Male
0301 basic medicine
Pathology
Cohort Studies
Pathogenesis
0302 clinical medicine
Genotype
CTLA-4 Antigen
Gray Matter
NCAN
Research Articles
General Neuroscience
Brain
Kv Channel-Interacting Proteins
Middle Aged
Fas receptor
Oligodendroglia
Disease Progression
Female
Autopsy
medicine.symptom
Research Article
Adult
medicine.medical_specialty
Multiple Sclerosis
Monosaccharide Transport Proteins
CLEC16A
Single-nucleotide polymorphism
Neuropathology
Polymorphism, Single Nucleotide
Pathology and Forensic Medicine
Lesion
03 medical and health sciences
medicine
Humans
Genetic Predisposition to Disease
Lectins, C-Type
fas Receptor
Aged
neuropathology
business.industry
Multiple sclerosis
FAS
medicine.disease
030104 developmental biology
Neurology (clinical)
business
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 10156305
- Database :
- OpenAIRE
- Journal :
- Brain Pathology, 30, 106-119. Wiley-Blackwell, Fransen, N L, Crusius, J B A, Smolders, J, Mizee, M R, van Eden, C G, Luchetti, S, Remmerswaal, E B M, Hamann, J, Mason, M R J & Huitinga, I 2020, ' Post-mortem multiple sclerosis lesion pathology is influenced by single nucleotide polymorphisms ', Brain Pathology, vol. 30, no. 1, pp. 106-119 . https://doi.org/10.1111/bpa.12760, Brain Pathology (Zurich, Switzerland), Brain Pathology, 30(1), 106-119. Wiley-Blackwell, Brain pathology (Zurich, Switzerland), 30(1), 106-119. Wiley-Blackwell
- Accession number :
- edsair.doi.dedup.....66b960a828b808d216b01ff3ab5d911d