Digestive Diseases and Sciences

, Volume 55, Issue 12, pp 3488–3494 | Cite as

The Association of Inflammatory Bowel Disease and Mediterranean Fever Gene (MEFV) Mutations in Turkish Children

  • Nuray UsluEmail author
  • Aysel Yüce
  • Hülya Demir
  • Inci N. Saltik-Temizel
  • Yusuf Usta
  • Engin Yilmaz
  • Nesrin Beşbaş
  • Figen Gürakan
  • Hasan Özen
  • Seza Özen
Original Article


Background and Aims

Familial Mediterranean fever (FMF) and inflammatory bowel disease (IBD) concordance has been investigated in a few studies. We investigated MEFV mutations and prevalence of FMF disease in Turkish children with IBD and their relationship with the disease severity.


Sixteen patients with ulcerative colitis (UC), 14 with Crohn’s disease (CD) and three with indeterminate colitis (IC) were enrolled in the study (median age 13 years, range 0.6–16 years, n = 19 boys). Demographic, clinical and laboratory characteristics of the patients were evaluated as well as the parameters of disease severity. All patients were screened for 12 common MEFV mutations.


MEFV mutations were detected in 17 of 66 (25.7%) alleles. Seven patients (four patients with CD, two with IC, and one with UC) were also diagnosed as FMF. FMF disease was found in seven of all IBD patients (21.2%) and four of them had CD. M694V was the leading mutation, and as a disease-causing mutation, it was found to be significantly more frequent in CD patients than UC patients (Fisher’s exact test P = 0.03). Demographics, laboratory evaluations, growth parameters, extraintestinal manifestations, and treatment with immunosuppressive agents other than steroids were comparable between the patients with and without FMF in most aspects.


Although this is a small cohort, disease-causing MEFV mutations and FMF disease rate were increased among our patients with IBD. The increase was prominent among CD patients, whereas in UC the rate was similar to the Turkish healthy control population.


Inflammatory bowel disease MEFV mutation FMF Children 



Part of this study was presented as a poster at the ESPGHAN 2007 meeting.


  1. 1.
    Dubinsky M. Special issues in pediatric inflammatory bowel disease. World J Gastroenterol. 2008;14:413–420.CrossRefPubMedGoogle Scholar
  2. 2.
    Hugot JP, Chamaillard M, Zouali H, et al. Association of NOD-2 leucine rich repeat variants with susceptibility to Crohn’s disease. Nature. 2001;411:599–603.CrossRefPubMedGoogle Scholar
  3. 3.
    Ogura Y, Bonen DK, Inohara N, et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature. 2001;411:603–606.CrossRefPubMedGoogle Scholar
  4. 4.
    Barrett JC, Hansoul S, Nicolae D, et al. Genome-wide association defines more than thirty distinct susceptibility loci for Crohn’s disease. Nat Genet. 2008;40:955–962.CrossRefPubMedGoogle Scholar
  5. 5.
    Livneh A, Langevitz P, Zemer D, et al. Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum. 1997;40:1879–1885.CrossRefPubMedGoogle Scholar
  6. 6.
    Ozen S. Familial Mediterranean fever: revisiting an ancient disease. Eur J Pediatr. 2003;162:449–454.CrossRefPubMedGoogle Scholar
  7. 7.
    Ozen S, Aktay N, Lainka E, Duzova A, Bakkaloglu A, Kallinich T. Disease severity in children and adolescents with familial Mediterranean fever: a comparative study to explore environmental effects on a monogenic disease. Ann Rheum Dis. 2009;68:246–248.CrossRefPubMedGoogle Scholar
  8. 8.
    Ozen S, Hoffman HM, Frenkerl J, Kastner D. Familial Mediterranean fever (FMF) and beyond: a new horizon. Fourth international congress on the systemic autoinflammatory disease held in Bethesda, USA, 6–10 November 2005. Ann Rheum Dis. 2006;65:961–964.CrossRefPubMedGoogle Scholar
  9. 9.
    Turkish FMF study group. Familial Mediterranean fever (FMF) disease in Turkey. Medicine. 2005;84:1–11.CrossRefGoogle Scholar
  10. 10.
    Yilmaz E, Ozen S, Balci B, et al. Mutation frequency of familial Mediterranean fever and evidence for a high carrier rate in the Turkish population. Eur J Hum Genet. 2001;9:553–555.CrossRefPubMedGoogle Scholar
  11. 11.
    Ayaz NA, Ozen S, Bilginer Y, et al. MEFV mutations in systemic onset juvenile idiopathic arthritis. Rheumatology. 2009;48:23–25.CrossRefPubMedGoogle Scholar
  12. 12.
    Cattan D, Notarnicola C, Molinari N, Touitou I. Inflammatory bowel disease in non-Ashkenazi Jews with familial Mediterranean fever. Lancet. 2000;355:378–379.CrossRefPubMedGoogle Scholar
  13. 13.
    Fidder HH, Chowers Y, Ackerman Z, et al. The familial Mediterranean fever (MEFV) gene as a modifier of Crohn’s disease. Am J Gatroenterol. 2005;100:338–343.CrossRefGoogle Scholar
  14. 14.
    Fidder HH, Chowers Y, Lidar M, Sternberg M, Langevitz P, Livneh A. Crohn's disease in patients with familial Mediterranean fever. Medicine. 2002;81:411–416.CrossRefPubMedGoogle Scholar
  15. 15.
    Giaglis S, Mimidis K, Papadopoulos V, et al. 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? Dig Dis Sci. 2006;51:687–692.CrossRefPubMedGoogle Scholar
  16. 16.
    Ozen S, Bakkaloglu A, Yilmaz E, et al. Mutations in the gene for familial Mediterranean fever: do they predispose to inflammation? J Rheum. 2003;30:2014–2018.PubMedGoogle Scholar
  17. 17.
    Sari S, Egritas O, Dalgic B. The familial Mediterranean fever (MEFV) gene may be a modifier factor of inflammatory bowel disease in infancy. Eur J Pediatr. 2006;167:391–393.CrossRefGoogle Scholar
  18. 18.
    Yurtcu E, Gokcan H, Yilmaz U, Sahin FI. Detection of MEFV gene mutations in patients with inflammatory bowel disease. Genet Test Mol Biomarkers. 2009;13:87–90.CrossRefPubMedGoogle Scholar
  19. 19.
    Ben-Chetrit E, Backenroth R. Amyloidosis induced, end stage renal disease in patients with familial Mediterranean fever is highly associated with point mutations in the MEFV gene. Ann Rheum Dis. 2001;60:146–149.CrossRefPubMedGoogle Scholar
  20. 20.
    The French FMF. Consortium: a candidate gene for familial Mediterranean fever. Nat Genet. 1997;17:25–31.CrossRefGoogle Scholar
  21. 21.
    The International FMF Consortium. Ancient missense mutations in a new member of RoRet gene family are likely to cause familial Mediterranean fever. Cell. 1997;90:797–807.CrossRefGoogle Scholar
  22. 22.
    Chae JJ, Wood G, Masters SL, et al. The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 modulate IL-1 beta production. Proc Natl Acad Sci USA. 2006;103:9982–9987.CrossRefPubMedGoogle Scholar
  23. 23.
    Kalyoncu M, Acar BC, Cakar N, et al. Are carriers for MEFV mutations “healthy”? Clin Exp Rheumatol. 2006;24:120–122.Google Scholar
  24. 24.
    IBD Working Group of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. Inflammatory bowel disease in children and adolescents: recommendations for diagnosis—the Porto criteria. J Pediatr Gastroenterol Nutr. 2005;41:1–7.CrossRefGoogle Scholar
  25. 25.
    North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition: Colitis Foundation of America, Bousvaros A, Antonioli DA, Colletti RB, et al. Differentiating ulcerative colitis from Crohn’s disease in children and young adults: report of a working group of the North American society for pediatric gastroenterology, hepatology and the Crohn’s and colitis foundation of America. J Pediatr Gastroenterol Nutr. 2007;44:653–674.CrossRefPubMedGoogle Scholar
  26. 26.
    Hyams JS, Ferry GD, Mandel FS, et al. Development and validation of a pediatric Crohn’s disease activity index. J Pediatr Gastroenterol Nutr. 1991;12:439–447.PubMedGoogle Scholar
  27. 27.
    Turner D, Otley AR, Mack D, et al. Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study. Gastroenterology. 2007;133:423–432.CrossRefPubMedGoogle Scholar
  28. 28.
    Yalcinkaya F, Ozcakar ZB, Kasapcopur O, et al. Prevalence of MEFV gene mutations in childhood polyarteris nodosa. J Pediatr. 2007;151:675–678.CrossRefPubMedGoogle Scholar
  29. 29.
    Church LD, Cook GP, McDermott MF. Primer: inflammasomes and interleukin 1beta in inflammatory disorders. Nat Clin Pract Rheumatol. 2008;4:34–42.CrossRefPubMedGoogle Scholar
  30. 30.
    Gershoni Baruch R, Broza Y, Brik R. Prevalence and significance of mutations in the familial Mediterranean fever gene in Henoch-Schönlein purpura. J Pediatr. 2003;143:658–661.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Nuray Uslu
    • 1
    Email author
  • Aysel Yüce
    • 1
  • Hülya Demir
    • 1
  • Inci N. Saltik-Temizel
    • 1
  • Yusuf Usta
    • 2
  • Engin Yilmaz
    • 3
  • Nesrin Beşbaş
    • 4
  • Figen Gürakan
    • 1
  • Hasan Özen
    • 1
  • Seza Özen
    • 4
  1. 1.Department of Pediatrics, Gastroenterology, Hepatology and Nutrition Unit, Faculty of MedicineHacettepe UniversityAnkaraTurkey
  2. 2.Department of Pediatrics, Gastroenterology, Hepatology and Nutrition UnitMersin UniversityMersinTurkey
  3. 3.Department of Medical Biology, Faculty of MedicineHacettepe UniversityAnkaraTurkey
  4. 4.Department of Pediatrics, Nephrology and Rheumatology Unit, Faculty of MedicineHacettepe UniversityAnkaraTurkey

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