Exploratory epigenetic analysis of host gene–dependent regulation of miR-197-3p in familial Mediterranean fever

Background. Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disease caused by mutations in the Mediterranean Fever (MEFV) gene. Despite its monogenic basis, FMF shows marked clinical heterogeneity, suggesting additional regulatory mechanisms. This exploratory study aimed to investigate host gene–dependent mechanisms underlying altered miR-197-3p expression in FMF. Materials and Methods. Peripheral blood mononuclear cells from homozygous FMF patients (n=6) and matched healthy controls (n=6) were analyzed. miR-197-3p expression was quantified using RT-qPCR. DNA methylation patterns in regulatory regions of the GNAI3 promoter and the MIR197 upstream candidate regulatory region were assessed by bisulfite sequencing. Results. miR-197-3p expression was significantly reduced in FMF patients compared with controls, as expected. No evidence supporting regulation through the MIR197 upstream candidate regulatory region was observed. Differential methylation within the GNAI3 promoter was statistically significant (p = 0.0093), supporting biological relevance despite the limited cohort size. Conclusion. These pilot findings provide preliminary molecular evidence supporting host gene–dependent regulation of miR-197-3p in FMF. Given the small cohort size, these findings should be considered exploratory and require validation in larger, independent cohorts.