Increased Frequency of Mutations in the Gene Responsible for Familial Mediterranean Fever (MEFV) in a Cohort of Patients with Ulcerative Colitis: Evidence for a Potential Disease-Modifying Effect?

Abstract

The MEFV gene, responsible for familial Mediterranean fever (FMF), is involved in inflammatory reactions through altered leukocyte apoptosis, secretion of interleukin (IL)-1β, and activation of the NF-κB pathway. Ulcerative Colitis (UC) and FMF are both characterized by a recurrent pattern of presentation with periods of remission and flares associated with neutrophilic infiltration at the site of injury. The aim of this study was to investigate the possible correlation between UC and MEFV gene alterations. Twenty-five consecutive, first-diagnosed and untreated UC patients, 28 control patients with rheumatoid arthritis, and 65 normal individuals were analyzed. Nonisotopic RNase Cleavage Assay (NIRCA) was applied as a first-step mutational screening method of exons 10 and 2 of MEFV gene; direct sequencing was subsequently performed to confirm the results. MEFV mutations were identified in 7 (3 M694V/0, 2 M680I/0, 1 E148Q/E148Q, and 1 A744S/0) out of 25 UC patients versus 1 (M694V/0) out of 28 rheumatoid arthritis patients (P = .0199) and 1 (M694V/0) out of 65 healthy controls (P = .0004). Four out of 7 patients with MEFV mutations had inflammatory arthritis, a clinical finding that was not observed in the 18 UC patients with unmutated MEFV (P = .0028). Patients with UC almost universally carried the T A C G MEFV exon 2 haplotype in contrast with normal individuals (P < .0001) and FMF patients (P = .0310). In conclusion the increased frequency of mutations of MEFV in UC patients, especially in those with episodic arthritis, suggests a possible modifying effect of MEFV in the disease process and its localization within the joint. The difference in distribution of MEFV exon 2 haplotypes between UC patients and both FMF patients and normal individuals, suggests that UC patients constitute a genetically distinct population. Larger, longitudinal studies are needed to confirm these initial findings.

Association of familial Mediterranean fever in Turkish children with inflammatory bowel disease

“…Although it appeared that the same was not true for UC, UC was found with the highest rate when IBD accompanied FMF both in the study we conducted in 2012 (17) and in the study of Giaglis et al (14). The fact that we found that UC accompanied FMF with a high rate of 78.6% in our study supports these points.…”

“…The fact that MEFV gene mutations are found with an increasing frequency in these inflammatory diseases supports this (13). In previous studies, it was found that MEFV gene mutations were observed with a higher rate in patients with a diagnosis of IBD compared to the population and molecular analysis of the MEFV gene may be considerably beneficial in terms of clinical practices (13,14).…”

Familial Mediterranean Fever

“…Four of the five most common mutations are in exon 10 (M694V, V726A, M694I, and M680I) and one of them is in exon 2 (E148Q). These mutations, in particular those in exon 10, were found in all patients carrying a risk of disease, albeit at different rates (15,16,25,(33)(34)(35)(36)(37).…”

Association of Familial Mediterranean Fever and Crohn’s disease

“…MEVF mutasyonunun hastalığın kliniğini de etkilediği bildirilmiştir. AAA mutasyonu olan ÜK'li 7 olgunun dördünde artrit saptanırken AAA mutasyonu olmayan hiçbir ÜK'li olguda artrit saptanmamıştır [7].…”