THU0544 The importance of R202Q polymorphism in clinical expression of FMF: a single center cross-sectional study

Abstract

Background Familial Mediterranean fever (FMF) is an autosomal recessive inherited disease with recurrent fever and inflammatory episodes of serous membranes. The MEFV (Mediterranean fever) gene in the short arm of chromosome 16 is affected in the FMF. This gene encodes for a protein called 9Pyrin9. The erroneously synthesized Pyrin protein due to MEFV mutations is unable to control the post inflammatory process. Although there have been many efforts to find out genotype-phenotype association in FMF, no clear relationship has been clarified. Objectives In this study, the relationship between FMF clinical symptoms and MEFV gene mutations and polymorphism was investigated. Methods Total of 158 patients with FMF was included to the study that was conducted in a tertiary rheumatology outpatient clinic. The demographic and clinical features, as well as MEFV gene mutations were recorded in a “Patient Assessment Form”. The clinical status of the disease was evaluated with FMF-severity score-2 (F-SS-2). The associations between clinical features and genetic alterations were calculated with Pearson Chi-square test. Results The mean age of patients was 24.3±5.1, mean delay in diagnosis was 5.6±6.3 years, and 155 of the patients (%98.1) were male. The percentage of patients stating they use colchicine regularly was 136 (86.1%), and mean dose was 1.4±0.3 mg/day. The most frequent mutation was M694V (76.6%), and R202Q, M680I and E148Q were found in a descending order (60.8%, 19.0% and 13.9%, respectively). The FMF severity score was found to be higher in patients carrying M694V mutation (p=0.01). In comparison with negative family history for FMF, M694V was more prevalent in patients with positive family history (82.0% vs 67.2%, p=0.035). Besides, M694V mutation found to be associated with arthritis (p=0.045). E148Q mutation was associated with the history of orchitis (p=0.029). The most significant relation between E148Q and clinical feature was family history of hemodialysis (p=0.005). The prevalence of non-periodic myalgia was %34.2, and this symptom was not present in patients carrying V726A mutation (p=0.005). M694V/R202Q was the most prevalent compound heterozygosis and found in 16 patients (10.1%). This mutation (M694V/R202Q) was associated with fewer frequencies of myalgia and peritonitis, and with good response to colchicine. Conclusions The presence of R202Q polymorphism is associated with FMF, and should be considered in the routine genetic analysis of the disease. In our patients, its co-existence with M694V seems to be associated with good response to colchicine, and to alleviate the severity of the disease expression of M694V, which is known to be associated with severe course. References Mor A, Shinar Y, Zaks N, Langevitz P, Chetrit A, Shtrasburg S, Rabinovitz E, Livneh A. Evaluation of disease severity in familial Mediterranean fever. Semin Arthritis Rheum. 2005 Aug;35(1):57–64. Disclosure of Interest None declared