Post-mortem multiple sclerosis lesion pathology is influenced by single nucleotide polymorphisms
| Autor: | Nina L. Fransen, Inge Huitinga, Sabina Luchetti, Joost Smolders, Jörg Hamann, Jakob B.A. Crusius, Ester B. M. Remmerswaal, Mark R. Mizee, Matthew R. J. Mason, Corbert G. van Eden |
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| Přispěvatelé: | Netherlands Institute for Neuroscience (NIN), Medical Microbiology and Infection Prevention, Graduate School, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, APH - Aging & Later Life, APH - Mental Health, Experimental Immunology, AII - Inflammatory diseases |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
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 |
| Zdroj: | 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 |
| ISSN: | 1015-6305 |
| DOI: | 10.1111/bpa.12760 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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