title: Rare MEFV variants are not associated with risk to develop multiple sclerosis and severity of disease.
abstract: BACKGROUND
  Recent studies suggest an association between rare variants in Mediterranean fever (MEFV), the gene underlying the auto-inflammatory disorder Familial Mediterranean Fever (FMF), the risk to develop multiple sclerosis (MS) and severity of MS.
  
  
  OBJECTIVE
  The objective of this study is to investigate these findings in a Belgian MS population and to test for association with additional clinical parameters such as treatment response.
  
  
  METHODS
  MEFV was sequenced in a cohort of MS patients (N=94) suffering from auto-inflammatory symptoms, systemic side-effects upon interferon-beta (IFN-β) treatment, or patients in whom glatiramer acetate was started as first choice due to severe fatigue. Five rare non-synonymous variants were detected in this cohort and subsequently genotyped in 915 MS patients and 763 healthy controls.
  
  
  RESULTS
  We observed no association between these alleles and susceptibility to MS (p-value=0.99) or disease severity (p-value=0.78). However, we did observe a correlation between carrying an MEFV variant and the development of systemic side-effects upon IFN-β treatment (p-value=0.022).
  
  
  CONCLUSIONS
  In contrast to recent smaller studies, we did not find an association between carrying a rare variant in the MEFV gene and the risk to develop MS or disease severity. However, carrying rare variants in MEFV was associated with the development of severe systemic side-effects upon IFN-β treatment.
authors: Department of Neurosciences, Laboratory for Neuroimmunology, Section of Experimental Neurology, KU Leuven, Belgium.
authors: Ine
authors: I
authors: Pauwels
authors: Leentje
authors: L
authors: Cosemans
authors: Steven
authors: S
authors: Boonen
authors: Bénédicte
authors: B
authors: Dubois
authors: An
authors: A
authors: Goris
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects; D016899:Interferon-beta / Q000009:adverse effects; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000235:genetics*; D000071198:Pyrin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D003598:Cytoskeletal Proteins; D007155:Immunologic Factors; C000604192:MEFV protein, human; D000071198:Pyrin; D016899:Interferon-beta
keywords: IFN-β; Multiple sclerosis; genetics; immunology