Analysis of MEFV exon methylation and expression patterns in familial Mediterranean fever

The study group was composed of pediatric FMF patients (N = 51) and age-gender matched healthy controls (N = 21). The relative expression level of MEFV was assessed via quantitative real-time PCR (qRT-PCR) and bisulfite sequencing (BS) was performed to analyse the methylation level quantitatively.MEFV expression in FMF patients were decreased compared to healthy controls (P = 0.031). Methylation level of exon 2 of MEFV was found to be slightly higher in FMF patients compared to healthy controls (76% versus 74%) (P = 0.049). The expression level of the MEFV was negatively correlated with the methylation level of the CpG island in both FMF and healthy controls groups (cor = -0.29, P = 0.041) but more so in the FMF only group (cor = -0.36, P = 0.035).In this study, the relation between reduced MEFV expression level and FMF was confirmed. Observed slight increase in methylation in FMF patients, and correlation of methylation with expression might be indicative of its role in FMF, however a larger dataset is needed to confirm our preliminary findings.Familial Mediterranean Fever (FMF) is an autoinflammatory disease that commonly affects Mediterranean people; mostly Turks, Jews, Armenians and Arabs. Typical symptoms of the disease are recurrent attacks of fever, and the inflammation of serosal membranes with abdominal pain [1]. MEFV is the first identified inflammatory gene, which is responsible for FMF [2,3]. Approximately 70 variations on MEFV gene are related to FMF. The most common five mutations, M694V, M694I, M680I and V726A in exon10 and E148Q in exon 2, are attributed approximately %80 of disease associated alleles in FMF patients coming from Mediterranean ancestry with clear clinical criteria [4-6].MEFV gene encodes Pyrin/Marenostrin which is mainly expressed in neutrophils, eosinophils, cytokine activated monocytes, dendritic cells and synovial fibroblasts. Pyrin/Marenostrin has a role in inflammation by activation of caspase-1, which is responsible for the matu