Genetic and Epigenetic Features of Familial Mediterranean Fever: What is New?
Familial Mediterranean Fever and Genetic
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https://doi.org/10.5281/zenodo.11215800Keywords:
Familial Mediterranean Fever, FMF, MEFV gene, miRNAsAbstract
Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disorder characterized by recurrent fever episodes and systemic inflammation, primarily attributed to mutations in the Mediterranean Fever (MEFV) gene.
Genetic studies have identified various mutations in the MEFV gene, with notable variants such as V726A, M694V, M694I, M680I, and E148Q predominating in affected populations. The MEFV gene encodes the pyrin protein, crucial for inflammasome assembly and subsequent inflammatory responses. While biallelic mutations are typical in FMF, monoallelic carriers also exhibit phenotypic variability, suggesting the involvement of additional genetic and environmental factors. Epigenetic mechanisms, particularly DNA methylation and histone modifications, play pivotal roles in regulating gene expression and inflammatory pathways in FMF. Studies investigating DNA methylation patterns of the MEFV gene have yielded conflicting results regarding their association with disease severity and colchicine responsiveness. Furthermore, histone modifications, including acetylation and methylation, have been implicated in inflammasome activation and FMF pathophysiology, offering potential therapeutic targets.
MicroRNAs (miRNAs), crucial regulators of gene expression, have emerged as key players in FMF pathogenesis. Dysregulated miRNA expression profiles in FMF patients, particularly those homozygous for specific mutations, suggest their involvement in immune dysregulation and cytokine modulation. Moreover, miRNAs hold promise as diagnostic biomarkers and therapeutic targets, with potential implications for personalized treatment strategies.
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