Yüksel MARAŞ, Ali AKDOĞAN, Bünyamin KISACIK, Levent KILIÇ, Engin YILMAZ, Abdurrahman TUFAN, Umut KALYONCU, Şaziye Şule APRAŞ BİLGEN, Sedat KİRAZ, Ali İhsan ERTENLİ, Meral ÇALGÜNERİ

MEFV mutation frequency and effect on disease severity in ankylosing spondylitis

To define the frequency of familial Mediterranean fever gene (MEFV) mutations in ankylosing spondylitis (AS) and describe different clinical aspects of MEFV mutation carrier and noncarrier AS patients. Materials and methods: In 112 AS patients, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) scores were calculated. The frequencies of 12 different MEFV mutations were studied by multiplex polymerase chain reaction/reverse hybridization method and were compared to those of previously studied healthy controls for 5 common MEFV mutations. Results: MEFV mutations were identified in 46 of 224 (20%) alleles and in 39 (35%) of AS patients. The distribution of mutations was: M694V, 30% (14); E148Q, 30% (14); P369S, 17% (8); V726A, 13% (6); A744S, 8% (4); and K695R, 2% (1). There were no significant differences between MEFV mutation carriers and noncarriers with respect to sex, age of symptom onset, disease duration, peripheral joint involvement, acute phase reactant levels, and BASDAI and BASFI scores (P > 0.05 all). MEFV mutation allelic frequency was not different between AS patients and healthy controls after adjusting for mutations studied (34/224 versus 22/200; P > 0.05). Conclusion: Although we did not find significant clinical and laboratory differences between MEFV mutation carrier and noncarrier AS patients, further investigations are needed to define the impact of MEFV mutations on AS disease course.

Anahtar Kelimeler:

Key words: Familial Mediterranean fever, ankylosing spondylitis, familial Mediterranean fever gene, seronegative spondyloarthropathy

MEFV mutation frequency and effect on disease severity in ankylosing spondylitis

Keywords:

Key words: Familial Mediterranean fever, ankylosing spondylitis, familial Mediterranean fever gene, seronegative spondyloarthropathy,

PDF

___

Braun J. Axial spondyloarthritis: thoughts about nomenclature and treatment targets. Clin Exp Rheumatol 2012; 30: S132– S135.
Öztürk A, Özçakar B, Ekim M, Akar N. Is MEFV gene Arg202Gln (605 G>A) a disease-causing mutation? Turk J Med Sci 2008; 38: 205–208
Öztürk A, Elbosky E, Elsayed SM, Alhodhod M, Akar N. Mutational analysis of the MEFV gene in Egyptian patients with familial Mediterranean fever. Turk J Med Sci 2009; 39: 229–234.
Gershoni-Baruch R, Shinawi M, Leah K, Badarnah K, Brik R. Familial Mediterranean fever: prevalence, penetrance and genetic drift. Eur J Hum Genet 2001; 9: 634–637.
Akkoc N, Sari I, Akar S, Binicier O, Thomas MG, Weale ME, Birlik M, Savran Y, Onen F, Bradman N et al. Increased prevalence of M694V in patients with ankylosing spondylitis: additional evidence for a link with familial Mediterranean fever. Arthritis Rheum 2010; 62: 3059–3063.
Durmus D, Alayli G, Cengiz K, Yigit S, Canturk F, Bagci H. Clinical significance of MEFV mutations in ankylosing spondylitis. Joint Bone Spine 2009; 76: 260–264.
van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984; 27: 361–368.
Yilmaz E, Ozen S, Balci B, Duzova A, Topaloglu R, Besbas N, Saatci U, Bakkaloglu A, Ozguc M. 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.
Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol 1994; 21: 2286–2291.
Calin A, Garrett S, Whitelock H, Kennedy LG, O’Hea J, Mallorie P, Jenkinson T. A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol 1994; 21: 2281–2285.
Cinar M, Dinc A, Simsek I, Erdem H, Koc B, Pay S, Tunca Y, Kilic S, Gul D. The rate and significance of Mediterranean fever gene mutations in patients with ankylosing spondylitis: a three-month, longitudinal clinical study. Rheumatol Int 2008; 29: 37–42.
Akkoc N, Gul A. Familial Mediterranean fever and seronegative arthritis. Curr Rheumatol Rep 2011; 13: 388–394.
Sims AM, Timms AE, Bruges-Armas J, Burgos-Vargas R, Chou CT, Doan T, Dowling A, Fialho RN, Gergely P, Gladman DD et al. Prospective meta-analysis of interleukin 1 gene complex polymorphisms confirms associations with ankylosing spondylitis. Ann Rheum Dis 2008; 67: 1305–1309.
Ozkurede VU, Franchi L. Immunology in clinic review series; focus on autoinflammatory diseases: role of inflammasomes in autoinflammatory syndromes. Clin Exp Immunol 2012; 167: 382–390.
Uthman I, Hajj-Ali RA, Arayssi T, Masri AF, Nasr F. Arthritis in familial Mediterranean fever. Rheumatol Int 2001; 20: 145– 148.
Kaşifoğlu T, Çalışır C, Cansu D, Korkmaz C. The frequency of sacroiliitis in familial Mediterranean fever and the role of HLA-B27 and MEFV mutations in the development of sacroiliitis. Clin Rheumatol 2009; 28: 41–46.
Akar S, Soysal O, Balci A, Solmaz D, Gerdan V, Onen F, Tunca M, Akkoc N. High prevalence of spondyloarthritis and ankylosing spondylitis among familial Mediterranean fever patients and their first-degree relatives: further evidence for the connection. Arthritis Res Ther 2013; 15: R21.
Calguneri M, Kalyoncu U, Akdogan A, Karadag O, Maras Y, Kısacık B, Bilgen AS, Ertenli I, Kiraz S. Ankylosing spondylitis has a more severe disease course when coexist with Familial Mediterranean Fever. ACR/ARHP Annual Scientific Meeting, 10–15 November 2006, Washington, DC, USA. Abstract (514) L35.
Tufan A, Mercan R, Tezcan ME, Kaya A, Bitik B, Ozturk MA. Enthesopathy in patients with familial Mediterranean fever: increased prevalence in M694 V variant. Rheumatol Int 2013; 33: 1933–1937.
Touitou I. The spectrum of familial Mediterranean fever (FMF) mutations. Eur J Hum Genet 2001; 9: 473–483.
Olgun A, Akman S, Kurt I, Tuzun A, Kutluay T. MEFV mutations in familial Mediterranean fever: association of M694V homozygosity with arthritis. Rheumatol Int 2005; 25: 255–259.
Lidar M, Kedem R, Mor A, Levartovsky D, Langevitz P, Livneh A. Arthritis as the sole episodic manifestation of familial Mediterranean fever. J Rheumatol 2005; 32: 859–862.