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

Authors :
Maurizio A Leone
Nadia Barizzone
Federica Esposito
Ausiliatrice Lucenti
Hanne F Harbo
An Goris
Ingrid Kockum
Annette Bang Oturai
Elisabeth Gulowsen Celius
Inger L Mero
Bénédicte Dubois
Tomas Olsson
Helle Bach Søndergaard
Daniele Cusi
Sara Lupoli
Bettina Kulle Andreassen
International Multiple Sclerosis Genetics Consortium
Wellcome Trust Case Control Consortium
Kjell-Morten Myhr
Franca R Guerini
PROGEMUS Group
PROGRESSO Group
Giancarlo Comi
Filippo Martinelli-Boneschi
Sandra D'Alfonso
Source :
PLoS ONE, Vol 8, Iss 6, p e64408 (2013)
Publication Year :
2013
Publisher :
Public Library of Science (PLoS), 2013.

Abstract

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.

Subjects

Subjects :
Medicine
Science

Details

Language :
English
ISSN :
19326203
Volume :
8
Issue :
6
Database :
Directory of Open Access Journals
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
edsdoj.44de3b4f33644da9a40dda1f2382e94e
Document Type :
article
Full Text :
https://doi.org/10.1371/journal.pone.0064408