Association of genetic markers with CSF oligoclonal bands in multiple sclerosis patients.
2013
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 OCB2 (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=9.4610 27 ) outside the HLA region (65 Mb).
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