PLoS ONE (Jan 2013)

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,
  • 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

DOI
https://doi.org/10.1371/journal.pone.0064408
Journal volume & issue
Vol. 8, no. 6
p. e64408

Abstract

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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.