Alterations in KLRB1 gene expression and a Scandinavian multiple sclerosis association study of the KLRB1 SNP rs4763655

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 (P0.046, odds ratio1.06 (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 (P0.001), and the KLRB1 expression decreased significantly (P0.001) 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. © 2011 Macmillan Publishers Limited All rights reserved.