Effects of epigenetic regulation on phenotypical exspressivity in familial mediterranean fever

Familial Mediterranean Fever (FMF) is an autosomal recessively inherited disease which is characterized with periodic fever and inflammation of the serous membranes such as 'peritonitis', 'arthritis','pleuritis' and 'erysipelas-like erythema'. Patients with MEFV gene mutations show wide phenotypic variations and are diagnosed with FMF with different symptoms and severity. Quantitative measures of the products of transcriptions and translations of MEFV gene, investigating of the methylation status and determining the effect of these factors on phenotype was aimed in this study. For that purpose gene expression of the MEFV gene was measured at the level of mRNA and protein and the methylation rates were determined. Forty FMF patients who consulted in Dokuz Eylul University, Faculty of Medicine, Division of Pediatric Nephrology and 32 healthy children who consulted for control in various clinics in Dokuz Eylul University, Faculty of Medicine, Department of Pediatrics were included in the study. When the levels of MEFV gene expression were compared between patients and healthy controls, it was seen that the expression levels were statistically significantly lower in the patient group (p= 0.049). The pyrin levels were found statistically significantly lower in the patient group when compared with the controls (p=0.037). Methylation rates were observed higher in the patient group, but it was not statistically significant (p=0.376). Patients were divided into two groups as Group A1 (patients with 2 or more mutations of MEFV gene) and Group A2 (patients with only one mutation of MEFV gene). These two groups were compared in terms of disease onset, frequency of the attacks, treatment response, severity of fever, stomachache, chest pain, arthralgia and erysipelas-like erythema. Only the treatment response was found statistically significantly different in the Group 1 compared to Group 2 (p= 0.021). As the M694V mutation is the most frequent mutation in the Turkish population and it is related to the severity of FMF, the patients in Group 1 were divided into 2 groups as M694V homozygote and others. The clinical and laboratory findings were compared between groups. The methylation rate was found lower in the M694V homozygote group but it was not statistically significant. There was no statistically significant differences between groups in expression and pyrin levels.