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

Author

Listed:
  • 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
  • Sandra D'Alfonso

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.

Suggested Citation

  • 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 Du, 2013. "Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients," PLOS ONE, Public Library of Science, vol. 8(6), pages 1-5, June.
    • Handle: RePEc:plo:pone00:0064408
    DOI: 10.1371/journal.pone.0064408
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