Association of genetic markers with CSF oligoclonal bands in multiple sclerosis patients

• Published in: PloS one Vol. 8; no. 6; p. e64408
• Main Authors: 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, Myhr, Kjell-Morten, Guerini, Franca R, Comi, Giancarlo, Martinelli-Boneschi, Filippo, D'Alfonso, Sandra
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.06.2013; Public Library of Science (PLoS)
• Subjects: Adult; Analysis; Autoimmune diseases; Biology; Cerebrospinal fluid; Chromosome 6; Clinical medicine; Confidence limits; Consortia; Disease; Disease susceptibility; Drb1 protein; Ethics; Female; Genetic aspects; Genetic factors; Genetic Markers; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; Health sciences; Histocompatibility antigen HLA; HLA antigens; HLA-DRB1 Chains - genetics; Hospitals; Humans; IL12B protein; Interdisciplinary aspects; Interleukin 1; Laboratories; Male; Markers; Medical research; Medicin och hälsovetenskap; Medicine; Meta-analysis; Meta-Analysis as Topic; Middle Aged; Multiple sclerosis; Multiple Sclerosis - cerebrospinal fluid; Multiple Sclerosis - genetics; Musical groups; Neurology; Neurosciences; Oligoclonal Bands - cerebrospinal fluid; Patients; Polymorphism, Single Nucleotide; Review boards; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Young Adult; Norway
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0064408

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.