Association of genetic markers with CSF oligoclonal bands in multiple sclerosis patients.

• Main Authors: Maurizio A Leone, Nadia Barizzone, Federica Esposito, Ausiliatrice Lucenti, Hanne F Harbo, An Goris, Ingrid Kockum, Annette Bang Oturai, Elisabeth Gulowsen Celius, Inger L Mero, Bénédicte Dubois, Tomas Olsson, Helle Bach Søndergaard, Daniele Cusi, Sara Lupoli, Bettina Kulle Andreassen, International Multiple Sclerosis Genetics Consortium, Wellcome Trust Case Control Consortium 2, Kjell-Morten Myhr, Franca R Guerini, PROGEMUS Group, PROGRESSO Group, Giancarlo Comi, Filippo Martinelli-Boneschi, Sandra D'Alfonso
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2013-01-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC3681825?pdf=render

to explore the association between genetic markers and Oligoclonal Bands (OCB) in the Cerebro Spinal Fluid (CSF) of Italian Multiple Sclerosis patients.We genotyped 1115 Italian patients for HLA-DRB1*15 and HLA-A*02. In a subset of 925 patients we tested association with 52 non-HLA SNPs associated with MS susceptibility and we calculated a weighted Genetic Risk Score. Finally, we performed a Genome Wide Association Study (GWAS) with OCB status on a subset of 562 patients. The best associated SNPs of the Italian GWAS were replicated in silico in Scandinavian and Belgian populations, and meta-analyzed.HLA-DRB1*15 is associated with OCB+: p = 0.03, Odds Ratio (OR) = 1.6, 95% Confidence Limits (CL) = 1.1-2.4. None of the 52 non-HLA MS susceptibility loci was associated with OCB, except one SNP (rs2546890) near IL12B gene (OR: 1.45; 1.09-1.92). The weighted Genetic Risk Score mean was significantly (p = 0.0008) higher in OCB+ (7.668) than in OCB- (7.412) patients. After meta-analysis on the three datasets (Italian, Scandinavian and Belgian) for the best associated signals resulted from the Italian GWAS, the strongest signal was a SNP (rs9320598) on chromosome 6q (p = 9.4×10(-7)) outside the HLA region (65 Mb).genetic factors predispose to the development of OCB.