期刊
MULTIPLE SCLEROSIS JOURNAL
卷 21, 期 13, 页码 1670-1680出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/1352458514568174
关键词
Multiple sclerosis; genetic risk; genetic association; disease course; oligoclonal bands; IgG index; relapse rate
资金
- Research Fund KU Leuven [OT/11/087, CREA/14/023]
- Research Foundation Flanders [G073415N]
- MS-Liga Vlaanderen
- Belgian Neurological Society
- Belgian Charcot Foundation
- Biogen Idec Chair Translational Research in Multiple Sclerosis
- Teva Pharma Nederland
- Rotary Club Zaventem
Background: More than 100 common variants underlying multiple sclerosis (MS) susceptibility have been identified, but their effect on disease phenotype is still largely unknown. Objective: The objective of this paper is to assess whether the cumulative genetic risk score of currently known susceptibility variants affects clinical presentation. Methods: A cumulative genetic risk score was based on four human leukocyte antigen (HLA) and 106 non-HLA risk loci genotyped or imputed in 842 Belgian MS patients and 321 controls. Non-parametric analyses were applied. Results: An increased genetic risk is observed for MS patients, including subsets such as oligoclonal band-negative and primary progressive MS patients, compared to controls. Within the patient group, a stronger association between HLA risk variants and the presence of oligoclonal bands, an increased immunoglobulin G (IgG) index and female gender was apparent. Results suggest an association between a higher accumulation of non-HLA risk variants and increased relapse rate as well as shorter relapse-free intervals after disease onset. Conclusion: MS patients display a significantly increased genetic risk compared to controls, irrespective of disease course or presence of oligoclonal bands. Whereas the cumulative burden of non-HLA risk variants appears to be reflected in the relapses of MS patients, the HLA region influences intrathecal IgG levels.
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