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Genetic variants of CC chemokine genes in experimental autoimmune encephalomyelitis, multiple sclerosis and rheumatoid arthritis.
Genes Immun 2010; 11(2):142-54GI

Abstract

Multiple sclerosis (MS) is a complex disorder of the central nervous system, causing inflammation, demyelination and axonal damage. A limited number of genetic risk factors for MS have been identified, but the etiology of the disease remains largely unknown. For the identification of genes regulating neuroinflammation we used a rat model of MS, myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), and carried out a linkage analysis in an advanced intercross line (AIL). We thereby redefine the Eae18b locus to a 0.88 Mb region, including a cluster of chemokine genes. Further, we show differential expression of Ccl2, Ccl11 and Ccl11 during EAE in rat strains with opposite susceptibility to EAE, regulated by genotype in Eae18b. The human homologous genes were tested for association to MS in 3841 cases and 4046 controls from four Nordic countries. A haplotype in CCL2 and rs3136682 in CCL1 show a protective association to MS, whereas a haplotype in CCL13 is disease predisposing. In the HLA-DRB1* 15 positive subgroup, we also identified an association to a risk haplotype in CCL2, suggesting an influence from the human leukocyte antigen (HLA) locus. We further identified association to rheumatoid arthritis in CCL2, CCL8 and CCL13, indicating common regulatory mechanisms for complex diseases.

Authors+Show Affiliations

Neuroimmunology Unit, Department of Clinical Neuroscience, Center of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. johan.ockinger@ki.seNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19865101

Citation

Ockinger, J, et al. "Genetic Variants of CC Chemokine Genes in Experimental Autoimmune Encephalomyelitis, Multiple Sclerosis and Rheumatoid Arthritis." Genes and Immunity, vol. 11, no. 2, 2010, pp. 142-54.
Ockinger J, Stridh P, Beyeen AD, et al. Genetic variants of CC chemokine genes in experimental autoimmune encephalomyelitis, multiple sclerosis and rheumatoid arthritis. Genes Immun. 2010;11(2):142-54.
Ockinger, J., Stridh, P., Beyeen, A. D., Lundmark, F., Seddighzadeh, M., Oturai, A., ... Olsson, T. (2010). Genetic variants of CC chemokine genes in experimental autoimmune encephalomyelitis, multiple sclerosis and rheumatoid arthritis. Genes and Immunity, 11(2), pp. 142-54. doi:10.1038/gene.2009.82.
Ockinger J, et al. Genetic Variants of CC Chemokine Genes in Experimental Autoimmune Encephalomyelitis, Multiple Sclerosis and Rheumatoid Arthritis. Genes Immun. 2010;11(2):142-54. PubMed PMID: 19865101.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic variants of CC chemokine genes in experimental autoimmune encephalomyelitis, multiple sclerosis and rheumatoid arthritis. AU - Ockinger,J, AU - Stridh,P, AU - Beyeen,A D, AU - Lundmark,F, AU - Seddighzadeh,M, AU - Oturai,A, AU - Sørensen,P S, AU - Lorentzen,A R, AU - Celius,E G, AU - Leppä,V, AU - Koivisto,K, AU - Tienari,P J, AU - Alfredsson,L, AU - Padyukov,L, AU - Hillert,J, AU - Kockum,I, AU - Jagodic,M, AU - Olsson,T, Y1 - 2009/10/29/ PY - 2009/10/30/entrez PY - 2009/10/30/pubmed PY - 2010/6/15/medline SP - 142 EP - 54 JF - Genes and immunity JO - Genes Immun. VL - 11 IS - 2 N2 - Multiple sclerosis (MS) is a complex disorder of the central nervous system, causing inflammation, demyelination and axonal damage. A limited number of genetic risk factors for MS have been identified, but the etiology of the disease remains largely unknown. For the identification of genes regulating neuroinflammation we used a rat model of MS, myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), and carried out a linkage analysis in an advanced intercross line (AIL). We thereby redefine the Eae18b locus to a 0.88 Mb region, including a cluster of chemokine genes. Further, we show differential expression of Ccl2, Ccl11 and Ccl11 during EAE in rat strains with opposite susceptibility to EAE, regulated by genotype in Eae18b. The human homologous genes were tested for association to MS in 3841 cases and 4046 controls from four Nordic countries. A haplotype in CCL2 and rs3136682 in CCL1 show a protective association to MS, whereas a haplotype in CCL13 is disease predisposing. In the HLA-DRB1* 15 positive subgroup, we also identified an association to a risk haplotype in CCL2, suggesting an influence from the human leukocyte antigen (HLA) locus. We further identified association to rheumatoid arthritis in CCL2, CCL8 and CCL13, indicating common regulatory mechanisms for complex diseases. SN - 1476-5470 UR - https://www.unboundmedicine.com/medline/citation/19865101/Genetic_variants_of_CC_chemokine_genes_in_experimental_autoimmune_encephalomyelitis_multiple_sclerosis_and_rheumatoid_arthritis_ L2 - http://dx.doi.org/10.1038/gene.2009.82 DB - PRIME DP - Unbound Medicine ER -