Digestive Diseases and Sciences

, Volume 51, Issue 4, pp 687–692

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?

  • Stavros Giaglis
  • Konstantinos Mimidis
  • Vassilios Papadopoulos
  • Konstantinos Thomopoulos
  • Prodromos Sidiropoulos
  • Stavros Rafail
  • Vassiliki Nikolopoulou
  • Eleni Fragouli
  • Georgios Kartalis
  • Athanasios Tzioufas
  • Dimitrios Boumpas
  • Konstantinos Ritis
Inflammatory Bowel Disease

DOI: 10.1007/s10620-006-3192-1

Cite this article as:
Giaglis, S., Mimidis, K., Papadopoulos, V. et al. Dig Dis Sci (2006) 51: 687. doi:10.1007/s10620-006-3192-1
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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-κ 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. MEFVmutations 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 MEFVmutations 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.

Key Words

MEFVFMFulcerative colitisextraintestinal manifestations

Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Stavros Giaglis
    • 1
  • Konstantinos Mimidis
    • 1
  • Vassilios Papadopoulos
    • 1
  • Konstantinos Thomopoulos
    • 2
  • Prodromos Sidiropoulos
    • 3
  • Stavros Rafail
    • 1
  • Vassiliki Nikolopoulou
    • 2
  • Eleni Fragouli
    • 3
  • Georgios Kartalis
    • 1
  • Athanasios Tzioufas
    • 4
  • Dimitrios Boumpas
    • 3
  • Konstantinos Ritis
    • 1
    • 5
  1. 1.First Division of Internal MedicineDemocritus University of ThraceAlexandroupolis
  2. 2.Department of Internal Medicine, Division of GastroenterologyUniversity of PatrasPatras
  3. 3.Department of Rheumatology, Clinical Immunology and AllergyUniversity of CreteHeraclion
  4. 4.Department of PathophysiologyAthens University Medical SchoolAthensGreece
  5. 5.AlexandroupolisGreece