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, L. Barcellos, D. Booth, M. Comabella, A. CompstonSandra D'Alfonso, P. De Jager, B. Fontaine, D. Hafler, J. Haines, S. L. Hauser, C. Hawkins, B. Hemmer, J. Hillert, A. Ivinson, R. Martin, F. Martinelli Boneschi, J. L. McCauley, J. Oksenberg, A. Oturai, N. Patsopoulos, M. Pericak-Vance, J. Saarela, S. Sawcer, A. Spurkland, G. Stewart, F. Zipp, Kjell Morten Myhr, Franca R. Guerini, Paola Naldi, Daniela Galimberti, Elio Scarpini, Roberto Bergamaschi, Antonella Di Sapio, Domenico Caputo, Gabriella Rosso, Susanna Cordera, Paola Cavalla, Roberto Cavallo, Maria D. Benedetti, Marco Salvetti, Ruggero Capra, Angelo Ghezzi, Pietro Annovazzi, Gabriella Coniglio, Giuseppe Liberatore, Mariaemma Rodegher, Lucia Moiola, Bruno Colombo, Marta Radaelli, Paolo Rossi, Vittorio Martinelli, Giancarlo Comi, Filippo Martinelli-Boneschi

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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.

Original languageEnglish (US)
Article numbere64408
JournalPloS one
Volume8
Issue number6
DOIs
StatePublished - Jun 13 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Leone, M. A., Barizzone, N., Esposito, F., Lucenti, A., Harbo, H. F., Goris, A., Kockum, I., Oturai, A. B., Celius, E. G., Mero, I. L., Dubois, B., Olsson, T., Søndergaard, H. B., Cusi, D., Lupoli, S., Andreassen, B. K., Barcellos, L., Booth, D., Comabella, M., ... Martinelli-Boneschi, F. (2013). Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients. PloS one, 8(6), [e64408]. https://doi.org/10.1371/journal.pone.0064408