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PLoS One. 2013 Jun 13;8(6):e64408. doi: 10.1371/journal.pone.0064408. Print 2013.

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

Author information

1
MS Centre, SCDU Neurology, AOU Maggiore della Carità, Novara, Italy. maurizio.leone@maggioreosp.novara.it

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.

PMID:
23785401
PMCID:
PMC3681825
DOI:
10.1371/journal.pone.0064408
[Indexed for MEDLINE]
Free PMC Article

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