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

Leone, Maurizio A.; Barizzone, Nadia; Esposito, Federica; Lucenti, Ausiliatrice; Harbo, Hanne F.; Goris, An; Kockum, Ingrid; Oturai, Annette Bang; Celius, Elisabeth Gulowsen; Mero, Inger L.; Dubois, Bénédicte; Olsson, Tomas; Søndergaard, Helle Bach; Cusi, Daniele; Lupoli, Sara; Andreassen, Bettina Kulle; Barcellos, L.; Booth, D.; Comabella, M.; Compston, A.; D'Alfonso, Sandra; De Jager, P.; Fontaine, B.; Hafler, D.; Haines, J.; Hauser, S. L.; Hawkins, C.; Hemmer, B.; Hillert, J.; Ivinson, A.; Martin, Rossella; Martinelli Boneschi, F.; Mccauley, J. L.; Oksenberg, J.; Oturai, A.; Patsopoulos, N.; Pericak-Vance, M.; Saarela, J.; Sawcer, S.; Spurkland, A.; Stewart, G.; Zipp, F.; Myhr, Kjell-Morten; Guerini, Franca R.; Naldi, Paola; Galimberti, Daniela; Scarpini, Elio; Bergamaschi, Roberto; Di Sapio, Antonella; Caputo, Domenico; Rosso, Gabriella; Cordera, Susanna; Cavalla, Paola; Cavallo, Roberto; Benedetti, Maria D.; Salvetti, Marco; Capra, Ruggero; Ghezzi, Angelo; Annovazzi, Pietro; Coniglio, Gabriella; Liberatore, Giuseppe; Rodegher, Mariaemma; Moiola, Lucia; Colombo, Bruno; Radaelli, Marta; Rossi, Paolo; Martinelli, Vittorio; Comi, Giancarlo; Martinelli-Boneschi, Filippo

doi:10.1371/journal.pone.0064408

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.

Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients / Leone, Maurizio A.; Barizzone, Nadia; Esposito, Federica; Lucenti, Ausiliatrice; Harbo, Hanne F.; Goris, An; Kockum, Ingrid; Oturai, Annette Bang; Celius, Elisabeth Gulowsen; Mero, Inger L.; Dubois, Bénédicte; Olsson, Tomas; Søndergaard, Helle Bach; Cusi, Daniele; Lupoli, Sara; Andreassen, Bettina Kulle; Barcellos, L.; Booth, D.; Comabella, M.; Compston, A.; D'Alfonso, Sandra; De Jager, P.; Fontaine, B.; Hafler, D.; Haines, J.; Hauser, S. L.; Hawkins, C.; Hemmer, B.; Hillert, J.; Ivinson, A.; Martin, Rossella; Martinelli Boneschi, F.; Mccauley, J. L.; Oksenberg, J.; Oturai, A.; Patsopoulos, N.; Pericak-Vance, M.; Saarela, J.; Sawcer, S.; Spurkland, A.; Stewart, G.; Zipp, F.; Myhr, Kjell-Morten; Guerini, Franca R.; Naldi, Paola; Galimberti, Daniela; Scarpini, Elio; Bergamaschi, Roberto; Di Sapio, Antonella; Caputo, Domenico; Rosso, Gabriella; Cordera, Susanna; Cavalla, Paola; Cavallo, Roberto; Benedetti, Maria D.; Salvetti, Marco; Capra, Ruggero; Ghezzi, Angelo; Annovazzi, Pietro; Coniglio, Gabriella; Liberatore, Giuseppe; Rodegher, Mariaemma; Moiola, Lucia; Colombo, Bruno; Radaelli, Marta; Rossi, Paolo; Martinelli, Vittorio; Comi, Giancarlo; Martinelli-Boneschi, Filippo. - In: PLOS ONE. - ISSN 1932-6203. - 8:6(2013), pp. 1-5. [10.1371/journal.pone.0064408]