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Familial Mediterranean fever-associated mutation pyrin E148Q as a potential risk factor for multiple sclerosis
T Kümpfel1, L-A Gerdes, T Wacker
1Institute of Clinical Neuroimmunology - Großhadern, Ludwig-Maximilians University of Munich, Germany. tania.kuempfel@med.uni-muenchen.de
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.
Insights
Familial Mediterranean fever (FMF) gene mutations, particularly E148Q, may increase multiple sclerosis (MS) susceptibility in Germany. Further research is needed to confirm this association and its implications for MS risk.
Area of Science:
- Genetics
- Immunology
- Neurology
Background:
- Familial Mediterranean fever (FMF) is an inherited autoinflammatory disorder caused by MEFV gene mutations.
- Previous studies suggest a potential link between FMF and multiple sclerosis (MS) in Turkish and Israeli populations.
Purpose of the Study:
- To determine the prevalence of MEFV gene mutations in German individuals with MS.
- To investigate the association between specific MEFV mutations (E148Q, K695R) and MS in a German cohort.
Main Methods:
- Genotyping of MEFV exons 2, 3, and 10 in 157 MS patients (group 1).
- Screening for E148Q and K695R mutations in 260 MS patients (group 2) and 400 controls.
- Analysis of mutation co-segregation with MS in affected families.
Main Results:
- 12.1% of MS patients in group 1 carried an MEFV mutation, predominantly E148Q.
- 15 of 19 mutation carriers reported FMF-suggestive symptoms.
- E148Q mutation showed co-segregation with MS in three families (p=0.026).
- No significant difference in E148Q/K695R frequencies between MS group 2 and controls, but high prevalence in the German population.
Conclusions:
- The MEFV gene is a potential contributor to MS susceptibility.
- The pyrin E148Q mutation is a candidate risk factor for MS, warranting further investigation.
- The high frequency of MEFV mutations in the German population merits attention.
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