Research: Osteopontin an MS susceptibility variant

Comi C, Cappellano G, Chiocchetti A, Orilieri E, Buttini S, Ghezzi L, Galimberti D, Guerini F, Barizzone N, Perla F, Leone M, D'Alfonso S, Caputo D, Scarpini E, Cantello R, Dianzani U. The impact of osteopontin gene variations on multiple sclerosis development and progression. Clin Dev Immunol. 2012;2012:212893. Epub 2012 Sep 11.
 
Osteopontin is a proinflammatory molecule, modulating TH1 and TH17 responses. Several reports suggest its involvement in multiple sclerosis (MS) pathogenesis. We previously reported that OPN gene variations at the 3' end are a predisposing factor for MS development and evolution. In this paper, we extended our analysis to a gene variation at the 5' end on the -156G > GG single nucleotide polymorphism (SNP) and replicated our previous findings at the 3' end on the +1239A > C SNP. We found that only +1239A > C SNP displayed a statistically significant association with MS development, but both +1239A > C and -156G > GG had an influence on MS progression, since patients homozygous for both +1239A and -156GG alleles displayed slower progression of disability and slower switch to secondary progression than those carrying +1239C and/or -156G and those homozygous for +1239A only. Moreover, patients homozygous for +1239A also displayed a significantly lower relapse rate than those carrying +1239C, which is in line with the established role of OPN in MS relapses.
Osteopontin (OPN), also known as bone sialoprotein I (BSP-1 or BNSP), early T-lymphocyte activation (ETA-1). Osteopontin (OPN) is expressed in a range of immune cells, including macrophages, neutrophils, dendritic cells, and T and B cells, with varying kinetics. OPN is reported to act as an immune modulator in a variety of manners. Firstly, it has chemotactic properties, which promote cell recruitment to inflammatory sites. In addition, OPN mediates cell activation and cytokine production, as well as promoting cell survival by regulating apoptosis. There may be some genetic variants that can influence susceptibility

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