RGMA and IL21R show association with experimental inflammation and multiple sclerosis
| Autor: | Mohsen Khademi, Johnny C. Lorentzen, Rita Nohra, Erik Wallström, C. Smestad, Annette Bang Oturai, Amennai Daniel Beyeen, Ingrid Kockum, Lars Alfredsson, Maja Jagodic, Hanne F. Harbo, Melanie Thessen Hedreul, Jan Hillert, Finn Sellebjerg, Emilie Sundqvist, Jian Ping Guo, Tomas Olsson |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Encephalomyelitis Autoimmune Experimental Multiple Sclerosis Genetic Linkage medicine.medical_treatment Immunology Quantitative Trait Loci Single-nucleotide polymorphism Nerve Tissue Proteins GPI-Linked Proteins Polymorphism Single Nucleotide Myelin oligodendrocyte glycoprotein Genetics medicine Animals Genetics (clinical) biology Multiple sclerosis Haplotype Experimental autoimmune encephalomyelitis Membrane Proteins Repulsive guidance molecule A medicine.disease Rats Cytokine Haplotypes Interleukin-21 receptor biology.protein Female Receptors Interleukin-21 |
| Zdroj: | Genes and immunity. 11(4) |
| ISSN: | 1476-5470 |
| Popis: | Rat chromosome 1 harbors overlapping quantitative trait loci (QTL) for cytokine production and experimental models of inflammatory diseases. We fine-dissected this region that regulated cytokine production, myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), anti-MOG antibodies and pristane-induced arthritis (PIA) in advanced intercross lines (AILs). Analysis in the tenth and twelfth generation of AILs resolved the region in two narrow QTL, Eae30 and Eae31. Eae30 showed linkage to MOG-EAE, anti-MOG antibodies and levels of interleukin-6 (IL-6). Eae31 showed linkage to EAE, PIA, anti-MOG antibodies and levels of tumor necrosis factor (TNF) and IL-6. Confidence intervals defined a limited set of potential candidate genes, with the most interesting being RGMA, IL21R and IL4R. We tested the association with multiple sclerosis (MS) in a Nordic case-control material. A single nucleotide polymorphism in RGMA associated with MS in males (odds ratio (OR)=1.33). Polymorphisms of RGMA also correlated with changes in the expression of interferon-gamma (IFN-gamma) and TNF in cerebrospinal fluid of MS patients. In IL21R, there was one positively associated (OR=1.14) and two protective (OR=0.87 and 0.68) haplotypes. One of the protective haplotypes correlated to lower IFN-gamma expression in peripheral blood mononuclear cells of MS patients. We conclude that RGMA and IL21R and their pathways are crucial in MS pathogenesis and warrant further studies as potential biomarkers and therapeutic targets. |
| Databáze: | OpenAIRE |
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