title: 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)-1beta, and activation of the NF-kappa B 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.
authors.affiliation: First Division of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Stavros
authors.initials: S
authors.lastname: Giaglis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Mimidis
authors.forename: Vassilios
authors.initials: V
authors.lastname: Papadopoulos
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Thomopoulos
authors.forename: Prodromos
authors.initials: P
authors.lastname: Sidiropoulos
authors.forename: Stavros
authors.initials: S
authors.lastname: Rafail
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Nikolopoulou
authors.forename: Eleni
authors.initials: E
authors.lastname: Fragouli
authors.forename: Georgios
authors.initials: G
authors.lastname: Kartalis
authors.forename: Athanasios
authors.initials: A
authors.lastname: Tzioufas
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Boumpas
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Ritis
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000453:epidemiology / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D010505:Familial Mediterranean Fever / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006115:Greece / Q000453:epidemiology; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011336:Probability; D000071198:Pyrin; D012016:Reference Values; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin