Familial Mediterranean fever-associated mutation pyrin E148Q as a potential risk factor for multiple sclerosis

• Published in: Multiple sclerosis Vol. 18; no. 9; pp. 1229 - 1238
• Main Authors: Kümpfel, T, Gerdes, L-A, Wacker, T, Blaschek, A, Havla, J, Krumbholz, M, Pöllmann, W, Feneberg, W, Hohlfeld, R, Lohse, P
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.09.2012; Sage Publications Ltd
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Case-Control Studies; Child; Child, Preschool; Cytoskeletal Proteins - genetics; Disability Evaluation; DNA Mutational Analysis; Exons; Familial Mediterranean Fever - diagnosis; Familial Mediterranean Fever - genetics; Familial Mediterranean Fever - immunology; Female; Gene Frequency; Genetic Predisposition to Disease; Germany; Humans; Infant; Male; Middle Aged; Multiple Sclerosis, Chronic Progressive - diagnosis; Multiple Sclerosis, Chronic Progressive - genetics; Multiple Sclerosis, Chronic Progressive - immunology; Multiple Sclerosis, Relapsing-Remitting - diagnosis; Multiple Sclerosis, Relapsing-Remitting - genetics; Multiple Sclerosis, Relapsing-Remitting - immunology; Mutation; Phenotype; Prospective Studies; Pyrin; Risk Assessment; Risk Factors; Young Adult; MEFV gene; susceptibility; multiple sclerosis; FMF
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1177/1352458512437813

Background: Familial Mediterranean fever (FMF) is an inherited autoinflammatory disease caused by mutations in the MEFV gene and characterized by recurrent febrile polyserositis. A possible association of FMF and multiple sclerosis (MS) has been suggested in cohorts from Turkey and Israel. Objective: The objective of this study was to investigate the prevalence of MEFV mutations in subjects with MS and in controls in Germany. Methods: One-hundred and fifty seven MS patients with at least one symptom or without symptoms suggestive of FMF from our outpatient clinic were investigated for mutations in exons 2, 3, and 10 of the MEFV gene (group 1). 260 independent MS patients (group 2) and 400 unrelated Caucasian controls (group 3) were screened selectively for the low-penetrance pyrin mutations E148Q and K695R Results: In group 1, 19 MS patients (12.1%) tested positive for a mutation in the MEFV gene, mainly the E148Q (n=7) substitution. Fifteen of the 19 mutation-positive individuals reported at least one symptom suggestive of FMF. In three cases, we could identify additional family members with MS. In these pedigrees, the E148Q exchange co-segregated with MS (p=0.026). Frequencies of the pyrin E148Q and K695R mutations were not statistically different between MS group 2 and controls but they occurred with a surprisingly high frequency in the German population. Conclusion: The MEFV gene appears to be another immunologically relevant gene locus which contributes to MS susceptibility. In particular, the pyrin E148Q mutation, which co-segregated with disease in three MS families, is a promising candidate risk factor for MS that should be further explored in larger studies.