title: Association of genetic markers with CSF oligoclonal bands in multiple sclerosis patients.
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).
  
  
  CONCLUSIONS
  genetic factors predispose to the development of OCB.
authors.affiliation: MS Centre, SCDU Neurology, AOU Maggiore della Carità, Novara, Italy. maurizio.leone@maggioreosp.novara.it
authors.forename: Maurizio A
authors.initials: MA
authors.lastname: Leone
authors.forename: Nadia
authors.initials: N
authors.lastname: Barizzone
authors.forename: Federica
authors.initials: F
authors.lastname: Esposito
authors.forename: Ausiliatrice
authors.initials: A
authors.lastname: Lucenti
authors.forename: Hanne F
authors.initials: HF
authors.lastname: Harbo
authors.forename: An
authors.initials: A
authors.lastname: Goris
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kockum
authors.forename: Annette Bang
authors.initials: AB
authors.lastname: Oturai
authors.forename: Elisabeth Gulowsen
authors.initials: EG
authors.lastname: Celius
authors.forename: Inger L
authors.initials: IL
authors.lastname: Mero
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Dubois
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.forename: Helle Bach
authors.initials: HB
authors.lastname: Søndergaard
authors.forename: Daniele
authors.initials: D
authors.lastname: Cusi
authors.forename: Sara
authors.initials: S
authors.lastname: Lupoli
authors.forename: Bettina Kulle
authors.initials: BK
authors.lastname: Andreassen
authors.forename: Kjell-Morten
authors.initials: KM
authors.lastname: Myhr
authors.forename: Franca R
authors.initials: FR
authors.lastname: Guerini
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Filippo
authors.initials: F
authors.lastname: Martinelli-Boneschi
authors.forename: Sandra
authors.initials: S
authors.lastname: D'Alfonso
mesh_terms: D000328:Adult; D005260:Female; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000235:genetics*; D043025:Oligoclonal Bands / Q000134:cerebrospinal fluid*; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D059811:HLA-DRB1 Chains; D043025:Oligoclonal Bands