Alteration of the microRNA expression profile in familial Mediterranean fever patients.

ABSTRACT

OBJECTIVES: Phenotypic heterogeneity in familial Mediterranean fever (FMF) disease indicated that FMF is not a simple monogenic disease. Therefore it has been suggested that epigenetic factors can be one of the reason for the variations. We undertook this study to test potential involvement of miRNAs in the pathogenesis of FMF. METHODS: miRNA array was performed on whole blood RNA samples from 6 healthy controls (-/-), 6 FMF patients (M694V/M694V), 6 carriers who displayed the disease phenotype (M694V/-) and 6 healthy carriers (M694V/-). The raw data was analysed by Multi Experiment Viewer (MeV) and candidate miRNAs were determined according to fold change (more than 2.0 or less than -2.0). The validation of differentially expressed miRNAs was done by qRT-PCR. Then we performed pathway analyses with using bioinformatics tools. RESULTS: 14 miRNAs were found to be significant among groups through the analysis with MeV. miR-20a-5p, miR-197-3p, let-7d-3p and miR-574-3p were found to be associated with inflammatory pathway related genes according to DAVID analysis. MiR-20a-5p (FDR 0,00, FCH 5.55) was significantly up regulated whereas miR-197-3p (FDR 0,00, FCH -2.27) was down regulated in homozygotes patients. Both let-7d-3p (FDR 0.00, FCH 28.75) and miR-574-3p (FDR 0.00, FCH 3.95) were up regulated in heterozygote patients group. CONCLUSIONS: We showed that there are several differentially expressed miRNAs both in homozygote and heterozygote FMF patients compared to controls and healthy carriers. Thus we suggest that these miRNAs, related with inflammatory pathways may be responsible for the expression of the disease in FMF.