RGD Reference Report - RGMA and IL21R show association with experimental inflammation and multiple sclerosis. - Rat Genome Database

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RGMA and IL21R show association with experimental inflammation and multiple sclerosis.

Authors: Nohra, R  Beyeen, AD  Guo, JP  Khademi, M  Sundqvist, E  Hedreul, MT  Sellebjerg, F  Smestad, C  Oturai, AB  Harbo, HF  Wallstrom, E  Hillert, J  Alfredsson, L  Kockum, I  Jagodic, M  Lorentzen, J  Olsson, T 
Citation: Nohra R, etal., Genes Immun. 2010 Jun;11(4):279-93. Epub 2010 Jan 14.
RGD ID: 6892695
Pubmed: PMID:20072140   (View Abstract at PubMed)
DOI: DOI:10.1038/gene.2009.111   (Journal Full-text)

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.

Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype

Human Phenotype
Objects Annotated

Genes (Rattus norvegicus)
Il21r  (interleukin 21 receptor)
Rgma  (repulsive guidance molecule BMP co-receptor a)

Genes (Mus musculus)
Il21r  (interleukin 21 receptor)
Rgma  (repulsive guidance molecule family member A)

Genes (Homo sapiens)
IL21R  (interleukin 21 receptor)
RGMA  (repulsive guidance molecule BMP co-receptor a)

Eae30  (Experimental allergic encephalomyelitis QTL 30)
Eae31  (Experimental allergic encephalomyelitis QTL 31)
Pia41  (Pristane induced arthritis QTL 41)

Additional Information