Abstract
Multiple sclerosis (MS) is a complex autoimmune disease affecting genetically susceptible individuals. A genome-wide association study performed by the International MS Genetics Consortium identified several putative susceptibility genes; among these, the KLRB1 gene is represented by the single-nucleotide polymorphism rs4763655. We could confirm a marginally significant association between rs4763655 and MS (P=0.046, odds ratio=1.06 (1.00–1.13)) in a large Scandinavian case–control study of 5367 MS patients and 4485 controls. The expression of KLRB1 in blood from MS patients was higher compared with healthy controls (P<0.001), and the KLRB1 expression decreased significantly (P<0.001) after interferon (IFN)-β treatment. KLRB1 was expressed in T and natural killer (NK) cells, and expression mainly decreased in NK cells in patients treated with IFN-β. Collectively, our results indicate that KLRB1 gene expression is altered in MS and likely to be involved in the pathogenesis of the disease, whereas rs4763655 in KLRB1 seems to have a minimal role in MS susceptibility.
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Acknowledgements
We thank Joy Mendel-Hartvig, Vibeke Fuglholt and Marie Koefoed for excellent laboratory work. The Danish MS Society, the Warwara Larsen Foundation, the Johnsen Foundation and The Danish Council for Strategic Research supported the Danish part of the study. The Research Council of Norway and South Eastern Norway Regional Health Authority supported the Norwegian part of the study. We thank the Norwegian Bone Marrow Donor Registry for collaboration in establishment of the Norwegian control material, and we acknowledge the Norwegian MS Register and Biobank for contribution of a proportion of the MS samples. Swedish Medical Research Council financed the Swedish part of the project (sample collection). Grants were provided by the Swedish Council for Working Life and Social Research, the fp6 EU program Neuropromise (LSHM-CT-2005-018637), Bibbi and Niels Jensens Foundation, Montel Williams Foundation, the Söderberg foundation and the Swedish Association for Persons with Neurological Disabilities.
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HBS, ML, JRC, EGC, IK, ILM, HFH and LB declare no conflict of interest. JH has received unrestricted research support from Biogen Idec, MercSerono and Bayer-Schering. TO has received unrestricted research support from Biogen Idec, Merck Serono, Sanofi-Aventis and Bayer Shering. KMM has received honoraria for lecturing and travel expenses for attending meetings, and research support from Biogen Idec, Bayer, Merck Serono or Sanofi-Aventis. FS has received honoraria for consulting or lecturing, travel grants or research grants from Bayer-Schering, Biogen Idec, Merck Serono, Novo Nordisk, Sanofi-Aventis, Schering-Plough and Teva; PSS has received funding, honoraria for consulting or lecturing or research grants from Baxter, Bayer-Schering, Biogen Idec, BioMS Medical, Merck Serono, Novartis, Sanofi-Aventis and Teva. ABO received travel grants and speakers honoraria from Biogen Idec, Bayer-Schering Pharma and Merck Serono.
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Søndergaard, H., Sellebjerg, F., Hillert, J. et al. Alterations in KLRB1 gene expression and a Scandinavian multiple sclerosis association study of the KLRB1 SNP rs4763655. Eur J Hum Genet 19, 1100–1103 (2011). https://doi.org/10.1038/ejhg.2011.88
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DOI: https://doi.org/10.1038/ejhg.2011.88
