Research: MERO and COLLEAGUES,

Listed in Issue 230

Abstract

MERO and COLLEAGUES,  (1)Department of Neurology, Oslo University Hospital, Ullevål, and Department of Medical Genetics, University of Oslo, Oslo, Norway searched for genetic differences in multiple sclerosis (MS) relating to the presence of oligoclonal bands (OCB) in cerebrospinal fluid (CSF).

Background

The presence of oligoclonal bands (OCB) in cerebrospinal fluid (CSF) is a typical finding in multiple sclerosis (MS).

Methodology

The authors applied data from Norwegian, Swedish and Danish (i.e. Scandinavian) MS patients from a genome-wide association study (GWAS) to search for genetic differences in MS relating to OCB status. GWAS data was compared in 1367 OCB positive and 161 OCB negative Scandinavian MS patients, and nine of the most associated SNPs were genotyped for replication in 3403 Scandinavian MS patients. HLA-DRB1 genotypes were analyzed in a subset of the OCB positive (n = 2781) and OCB negative (n = 292) MS patients and compared to 890 healthy controls.

Results

Results from the genome-wide analyses showed that single nucleotide polymorphisms (SNPs) from the HLA complex and six other loci were associated to OCB status. In SNPs selected for replication, combined analyses showed genome-wide significant association for two SNPs in the HLA complex; rs3129871 (p = 5.7×10(-15)) and rs3817963 (p = 5.7×10(-10)) correlating with the HLA-DRB1*15 and the HLA-DRB1*04 alleles, respectively. The researchers also found suggestive association to one SNP in the Calsyntenin-2 gene (p = 8.83×10(-7)). In HLA-DRB1 analyses HLA-DRB1*15∶01 was a stronger risk factor for OCB positive than OCB negative MS, whereas HLA-DRB1*04∶04 was associated with increased risk of OCB negative MS and reduced risk of OCB positive MS. Protective effects of HLA-DRB1*01∶01 and HLA-DRB1*07∶01 were detected in both groups. The groups were different with regard to age at onset (AAO), MS outcome measures and gender.

Conclusion

This study confirms both shared and distinct genetic risk for MS subtypes in the Scandinavian population defined by OCB status and indicates different clinical characteristics between the groups. This suggests differences in disease mechanisms between OCB negative and OCB positive MS with implications for patient management, which need to be further studied.

References

Mero IL(1), Gustavsen MW, Sæther HS, Flåm ST, Berg-Hansen P, Søndergaard HB, Jensen PE, Berge T, Bjølgerud A, Muggerud A, Aarseth JH; Collaborators: Barcellos L, Booth D, Comabella M, Compston A, D'Alfonso S, De Jager P, Fontaine B, Goris A, Hafler D, Haines J, Harbo HF, Hauser SL, Hawkins C, Hemmer B, Hillert J, Ivinson A, Kockum I, Martin R, Martinelli Boneschi F, McCauley JL, Oksenberg J, Olsson T, Oturai A, Patsopoulos N, Pericak-Vance M, Saarela J, Sawcer S, Spurkland A, Stewart G, Zipp F. International Multiple Sclerosis Genetics Consortium, Myhr KM, Celius EG, Sellebjerg F, Hillert J, Alfredsson L, Olsson T, Oturai AB, Kockum I, Lie BA, Andreassen BK, Harbo HF. Oligoclonal band status in Scandinavian multiple sclerosis patients is associated with specific genetic risk alleles.  PLoS One: 8(3):e58352. 2013. doi: 10.1371/journal.pone.0058352. Epub Mar 5 2013.

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