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 / M.A. Leone, N. Barizzone, F. Esposito, F. Lucenti, H.F. Harbo, A. Goris, I. Kockum, A.B. Oturai, E.G. Celius, I.L. Mero, B. Dubois, T. Olsson, H.B. Søndergaard, D. Cusi, S. Lupoli, B.K. Andreassen, International Multiple Sclerosis Genetics Consortium, Wellcome Trust Case Control Consortium 2, K.M. Myhr, F.R. Guerini, PROGEMUS Group, PROGRESSO Group, G. Comi, F. Martinelli-Boneschi, S. D'Alfonso. - In: PLOS ONE. - ISSN 1932-6203. - 8:6(2013 Jun). [Epub ahead of print]

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

D. Cusi;S. Lupoli;F. Martinelli-Boneschi;
2013-06

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.
Settore MED/14 - Nefrologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/221638
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