Background/Purpose:

Familial Mediterranean Fever (FMF) is an autoinflammatory disease caused by mutations in a single gene, the MEFV gene. The disease is very frequent among patients with an eastern European ancestry but may occur in much lesser frequencies in other ethnic groups as well. We present the disease characteristics in patients living in the eastern Mediterranean and how they compare to the eastern Mediterranean patients living in western Europe and to the Europeans.

Methods:

The data was extracted from the Eurofever project, that accomplished a multicenter registry for the autoinflammatory diseases in Europe and neighboring countries. From this registry 346 FMF patients whose diagnosis was confirmed were the subjects of this study. We developed a disease severity score that was modified from and harmonized the existing scores in the literature.

Results:

The disease manifestations such as fever, abdominal pain, acute phase reactants were similar in all patients. The genetics and demographic features with increased acute phase reactants were similar among eastern Mediterranean patients whether they lived in their countries or western European countries. The mutation distribution of the European patients displayed differences and they were diagnosed later. On the other hand when features suggesting a severe disease expression were analysed, the eastern Mediterranean patients living in Europe were significantly different than those living in their countries and were similar to European patients and displayed milder phenotypic manifestations, with less attacks, less arthritis and less chest pain. When multivariate analysis was applied to assess the effect of residence, not ethnicity but the  country of residence positively influenced the severity of disease presentation. Other independent variables were the presence of M694V (also on a.  single allele), a positive family history  together with disease delay.  

Conclusion: We clearly demonstrate the actual impact of environment and genetic factors on the expression of a monogenic disease. We suggest that since FMF is the disease of the innate immune system and since the mutated protein is a component of the inflammasome triggered by microbial products, environmental factors including diet have a significant effect. Epigenetic studies are now in order.

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« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/results-from-a-multicentre-international-registry-of-familial-mediterranean-fever-impact-of-genetic-and-environment-factors-on-the-expression-of-a-monogenic-disease-in-children/