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The presence of MEFV gene mutations in patients with primary osteoarthritis who require surgery

  • Yilmaz, Sedat (Division of Rheumatology, Gulhane School of Medicine) ;
  • Erdem, Hakan (Division of Rheumatology, Gulhane School of Medicine) ;
  • Tunay, Servet (Department of Orthopedic Surgery, Gulhane School of Medicine) ;
  • Torun, Deniz (Department of Medical Genetics, Gulhane School of Medicine) ;
  • Genc, Halil (Department of Internal Medicine, Gulhane School of Medicine) ;
  • Tunca, Yusuf (Department of Medical Genetics, Gulhane School of Medicine) ;
  • Karadag, Omer (Division of Rheumatology, Gulhane School of Medicine) ;
  • Simsek, Ismail (Division of Rheumatology, Gulhane School of Medicine) ;
  • Bahce, Muhterem (Department of Medical Genetics, Gulhane School of Medicine) ;
  • Pay, Salih (Division of Rheumatology, Gulhane School of Medicine) ;
  • Dinc, Ayhan (Division of Rheumatology, Gulhane School of Medicine)
  • Received : 2012.09.30
  • Accepted : 2013.03.15
  • Published : 2013.09.01

Abstract

Background/Aims: Chronic arthritis of familial Mediterranean fever (FMF) involves weight-bearing joints and can occur in patients without a history of acute attack. Our aim was to investigate a possible causal relationship between FMF and osteoarthritis in a population in which FMF is quite common. Methods: Patients with late stage primary osteoarthritis were enrolled, and five MEFV gene mutations were investigated. The frequency of MEFV gene mutations was compared among patients with osteoarthritis and a previous healthy group from our center. Results: One hundred patients with primary osteoarthritis and 100 healthy controls were studied. The frequency of MEFV gene mutations was significantly lower in the osteoarthritis group (9% vs. 19%). M694V was the most frequent mutation (5%) in the osteoarthritis group, whereas in the control group, E148Q was the most common (16%). In subgroup analyses, the mutation frequency of patients with hip osteoarthritis was not different from that of patients with knee osteoarthritis and controls (7.1%, 9.7%, and 19%, respectively). There were no differences among the three groups with respect to MEFV gene mutations other than E148Q (8.1% vs. 3.6%). E148Q was significantly lower in the osteoarthritis group than in the controls (16% vs. 1%), although the mutations did not differ between patients with knee osteoarthritis and controls. Conclusions: In a population with a high prevalence of MEFV gene mutations, we did not find an increased mutation rate in patients with primary osteoarthritis. Furthermore, we found that some mutations were significantly less frequent in patients with osteoarthritis. Although the number of patients studied was insufficient to claim that E148Q gene mutation protects against osteoarthritis, the potential of this gene merits further investigation.

Keywords

References

  1. Lawrence RC, Helmick CG, Arnett FC, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum 1998;41:778-799. https://doi.org/10.1002/1529-0131(199805)41:5<778::AID-ART4>3.0.CO;2-V
  2. Ehrlich GE. Osteoarthritis beginning with inflammation. Definitions and correlations. JAMA 1975;232:157- 159. https://doi.org/10.1001/jama.1975.03250020031020
  3. Heller H, Gafni J, Michaeli D, et al. The arthritis of familial Mediterranean fever (FMF). Arthritis Rheum 1966;9:1-17. https://doi.org/10.1002/art.1780090102
  4. Garcia-Gonzalez A, Weisman MH. The arthritis of familial Mediterranean fever. Semin Arthritis Rheum 1992;22:139-150. https://doi.org/10.1016/0049-0172(92)90014-5
  5. Sneh E, Pras M, Michaeli D, Shanin N, Gafni J. Protracted arthritis in familial Mediterranean fever. Rheumatol Rehabil 1977;16:102-106. https://doi.org/10.1093/rheumatology/16.2.102
  6. Younes M, Kahn MF, Meyer O. Hip involvement in patients with familial Mediterranean fever: a review of ten cases. Joint Bone Spine 2002;69:560-565. https://doi.org/10.1016/S1297-319X(02)00452-9
  7. Bhat A, Naguwa SM, Gershwin ME. Genetics and new treatment modalities for familial Mediterranean fever. Ann N Y Acad Sci 2007;1110:201-208. https://doi.org/10.1196/annals.1423.022
  8. Stehlik C, Fiorentino L, Dorfleutner A, et al. The PAAD/ PYRIN-family protein ASC is a dual regulator of a conserved step in nuclear factor kappaB activation pathways. J Exp Med 2002;196:1605-1615. https://doi.org/10.1084/jem.20021552
  9. Booth DR, Lachmann HJ, Gillmore JD, Booth SE, Hawkins PN. Prevalence and significance of the familial Mediterranean fever gene mutation encoding pyrin Q148. QJM 2001;94:527-531. https://doi.org/10.1093/qjmed/94.10.527
  10. Cosan F, Tozkir JD, Ustek D, Ocal L, Aral O, Gul A. Association of familial Mediterranean fever-related MEFV gene M694V mutation with ankylosing spondylitis. Arthritis Rheum 2006;54:S465-S466.
  11. Rabinovich E, Livneh A, Langevitz P, et al. Severe disease in patients with rheumatoid arthritis carrying a mutation in the Mediterranean fever gene. Ann Rheum Dis 2005;64:1009-1014. https://doi.org/10.1136/ard.2004.029447
  12. Rabinovich E, Shinar Y, Leiba M, Ehrenfeld M, Langevitz P, Livneh A. Common FMF alleles may predispose to development of Behcet's disease with increased risk for venous thrombosis. Scand J Rheumatol 2007;36:48-52. https://doi.org/10.1080/03009740600759639
  13. 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. https://doi.org/10.1007/s10620-006-3192-1
  14. Ozen S, Bakkaloglu A, Yilmaz E, et al. Mutations in the gene for familial Mediterranean fever: do they predispose to inflammation? J Rheumatol 2003;30:2014-2018.
  15. Neame RL, Muir K, Doherty S, Doherty M. Genetic risk of knee osteoarthritis: a sibling study. Ann Rheum Dis 2004;63:1022-1027. https://doi.org/10.1136/ard.2003.014498
  16. Lanyon P, Muir K, Doherty S, Doherty M. Assessment of a genetic contribution to osteoarthritis of the hip: sibling study. BMJ 2000;321:1179-1183. https://doi.org/10.1136/bmj.321.7270.1179
  17. Valdes AM, Spector TD. The contribution of genes to osteoarthritis. Med Clin North Am 2009;93:45-66. https://doi.org/10.1016/j.mcna.2008.08.007
  18. Valdes AM, Spector TD. The genetic epidemiology of osteoarthritis. Curr Opin Rheumatol 2010;22:139-143. https://doi.org/10.1097/BOR.0b013e3283367a6e
  19. Tunca M, Kirkali G, Soyturk M, Akar S, Pepys MB, Hawkins PN. Acute phase response and evolution of familial Mediterranean fever. Lancet 1999;353:1415.
  20. Lachmann HJ, Sengul B, Yavuzsen TU, et al. Clinical and subclinical inflammation in patients with familial Mediterranean fever and in heterozygous carriers of MEFV mutations. Rheumatology (Oxford) 2006;45:746-750. https://doi.org/10.1093/rheumatology/kei279
  21. 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. https://doi.org/10.1038/sj.ejhg.5200674
  22. Ben-Chetrit E, Lerer I, Malamud E, Domingo C, Abeliovich D. The E148Q mutation in the MEFV gene: is it a disease-causing mutation or a sequence variant? Hum Mutat 2000;15:385-386.
  23. Tchernitchko D, Legendre M, Cazeneuve C, Delahaye A, Niel F, Amselem S. The E148Q MEFV allele is not implicated in the development of familial Mediterranean fever. Hum Mutat 2003;22:339-340.
  24. Koc B, Oktenli C, Bulucu F, Karadurmus N, Sanisoglu SY, Gul D. The rate of pyrin mutations in critically ill patients with systemic inf lammatory response syndrome and sepsis: a pilot study. J Rheumatol 2007;34:2070-2075.

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