Evaluating the effects of micrornas on familial mediterranean fever

EVALUATING THE EFFECTS OF MICRORNAS ON FAMILIAL MEDITERRANEAN FEVER Introduction: Familial Mediterranean fever (FMF) is an autosomal recessive inherited autoinflammatory disorder that can result in attacks with accompanying recurrent episodes of fever, serositis, and skin rash. There is no specific laboratory test to diagnose the disease; therefore, it is diagnosed using clinical and developed diagnostic criteria. Molecular investigations help diagnose the disease; however, not all patients can be diagnosed molecularly. Many mutations have been observed in the MEFV gene responsible for FMF, the most common are M694V, M680I, V726A, and E148Q. The clinical characteristics of the disease are varied and the mutations are associated with the severity of the disease; however, the clinical characteristics could be different in patients with the same mutation. MicroRNAs (miRNAs) are small, single-stranded, endogenous, and noncoding molecules, which vary between 19-25 nucleotides in length. MiRNAs are known to play a significant role in cell growth, homeostasis, and immune functions, and are associated with many diseases ranging from cancer to inflammation. While there are various hypotheses about the pathogenesis of FMF, the reason is yet to be established clearly. This is a disease with no genotype-phenotype correlation and unexplained clinical differences. MiRNAs are demonstrated to be associated with a number of diseases as well as autoinflammatory disorders; however, no comprehensive study has revealed its association with FMF disease. In our study, we investigated the role of microRNAs in FMF. Methods: In our study, we included 51 patients with genetically diagnosed FMF who had clinical symptoms and 49 healthy volunteers. The expression levels of miRNAs obtained from plasmas were analyzed using real-time PCR. Fifteen miRNAs that were found to be associated with autoinflammatory diseases and have a part in immune response were evaluated between the two groups and within the patient group. Findings: The miRNA expression differences in the patient group and control group, which consisted of healthy individuals, were investigated. The patients were examined in two groups: those who took colchicine and those who did not. The expression levels of 11 miRNAs (miR-125a, miR-132, miR-146a, miR-155, miR-15a, miR-16, miR-181a, miR-21, miR-223, miR-26a, and miR-34a) in the patient group were significantly low, compared with the control group (p<0.05). The patient group was analyzed and compared within itself, and the expression levels of 5 miRNAs (miR-132, miR-15a, miR-181a, miR-23b, miR-26a) in the patients who took colchicine seemed to have increased significantly, compared with the patients who did not take colchicine (p<0.05). When compared with the control group, the expression levels of 5 miRNAs (miR-146a, miR-15a, miR-16, miR-26a, miR-34a) in the patients who took colchicine were significantly lower (p<0.05). Similarly, compared with the control group, the expression levels of 7 miRNAs (miR-146a, miR-132, miR-15a, miR-181a, miR-16, miR-26a, miR-21) in the patients who did not take colchicine were significantly lower (p<0.05). Furthermore, the attack patients were compared with the control group, and their expression levels of 4 miRNAs (miR-132, miR-15a, miR-21, miR-34a) were significantly lower (p<0.05). The expression levels of 9 miRNAs (miR-132, miR-146a, miR-15a, miR-16, miR-181a, miR-21, miR-223, miR-26a, miR-34a) in non-attack patients decreased significantly, compared with the control group (p<0.05). Conclusion: Our study demonstrates that miRNAs could be effective in the pathogenesis of FMF. Additionally, the miRNA expression differences among individuals could help discover different phenotypes. Keywords: MEFV, familial Mediterranean fever, microRNA