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Common mutations in the familial Mediterranean fever gene associate with rapid progression to disability in non-Ashkenazi Jewish multiple sclerosis patients

Genes & Immunity volume 4, pages 197–203 (2003)Cite this article

Abstract

Ancient founder mutations in the Mediterranean fever gene, MEFV, are associated with familial Mediterranean fever, a recessive, episodic, inflammatory disease. Since these mutations are reported to express with above normal levels of acute phase reactants in healthy heterozygotes we postulated that the heterozygous phenotype could aggravate the clinical expression of ongoing autoimmune diseases. This study evaluated progression to disability in relapsing–remitting multiple sclerosis (RR-MS) patients of non-Ashkenazi and Ashkenazi origin carrying an MEFV mutation, particularly the detrimental M694V, using the expanded disability status scale (EDSS). In the non-Ashkenazi patients group (n=48), carriers (n=17) presented with a two-fold higher fraction which reached EDSS=3.0 and 6.0 compared to noncarriers (n=31) despite a comparable mean of MS duration. The median time to reach EDSS=3.0 was 2 years in the carriers vs 10 years in noncarriers (P=0.007); The median time to reach EDSS=6.0 was 6 years vs 23 years, respectively (P=0.003). M694V heterozygous patients reached both EDSS milestones earlier than other patients. Progression to disability was not enhanced in Ashkenazi RR-MS carriers (n=12, noncarriers n=59). In conclusion, non-Asheknazi MS patients carrying one mutated MEFV gene, particularly M694V, expressed rapid progression to disability. The expressed mutation may increase inflammatory damage inflicted by autoimmune responses.

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Acknowledgements

The authors are grateful to Dr Art McMorris for helpful discussions and to Dr Dan Kastner, Dr Irun Cohen, and Dr Mordechai Pras for reviewing the manuscript. Supported by Grant No. 6279 from the Israeli Ministry of Science.

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Authors and Affiliations

  1. Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer, Israel

    Y Shinar, A Livneh, A Pinhasov & A Kogan

  2. Department of Statistics, Tel Aviv University, Israel

    Y Villa

  3. The Multiple Sclerosis Center, Sheba Medical Center, Tel Hashomer, Israel

    I Zeitoun & A Achiron

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  1. Y Shinar
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  2. A Livneh
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  4. A Pinhasov
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  5. I Zeitoun
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  6. A Kogan
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  7. A Achiron
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Correspondence to Y Shinar.

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Shinar, Y., Livneh, A., Villa, Y. et al. Common mutations in the familial Mediterranean fever gene associate with rapid progression to disability in non-Ashkenazi Jewish multiple sclerosis patients. Genes Immun 4, 197–203 (2003). https://doi.org/10.1038/sj.gene.6363967

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  • DOI: https://doi.org/10.1038/sj.gene.6363967

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