Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients

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, the International Multiple Sclerosis Genetics Consortium, the Wellcome Trust Case Control Consortium 2, Kjell-Morten Myhr, Franca R Guerini, the PROGEMUS Group, the PROGRESSO Group, Giancarlo Comi, Filippo Martinelli-Boneschi and Sandra D'Alfonso

PLOS ONE, 2013, vol. 8, issue 6, 1-5

Abstract: Objective: to explore the association between genetic markers and Oligoclonal Bands (OCB) in the Cerebro Spinal Fluid (CSF) of Italian Multiple Sclerosis patients. Methods: 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. Results: 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). Discussion: genetic factors predispose to the development of OCB.

Date: 2013
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0064408

DOI: 10.1371/journal.pone.0064408

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