Ayse Kevser DEMİR, Hülya DEVECİ, Zeliha Cansel ÖZMEN, Ayşe KEFELİ, Şafak ŞAHİN, Türker TAŞLIYURT, KÖKSAL DEVECİ

Ailevi Akdeniz Ateşi Genetik Özellikleri ve Sistemik Hastalıklarla İlişkisi

Amaç: Bu çalışma Ailevi Akdeniz Ateşi (AAA) tanısı olan hastaların genetik özelliklerini analiz etmeyi ve AAA’nın sistemik hastalıklarla ilişkisini değerlendirmeyi amaçlamaktadır. Gereç ve Yöntem: Çalışmada Ocak 2015 ve Mayıs 2018 arasında Tokat Gaziosmanpaşa Üniversitesi iç hastalıkları ve fizik tedavi polikliniklerine başvuran 277 AAA hastasının verileri geriye dönük olarak değerlendirildi. Tüm hastaların cinsiyeti, yaşı, AAA semptomları, eşlik eden sistemik hastalıkları ve mutasyon analizleri kaydedildi. Bulgular: Çalışmaya dahil edilen 277 AAA hastasının 176’sı (%63,5) kadın ve 101’i (%36,5) erkekti. Hastaların yaş ortalaması 33,6±11,8 idi. 277 AAA hastasının 170’inin (%61) mutasyon analizine ulaşıldı. 161 (%95) hastada mutasyon varlığı tespit edildi. En sık tespit edilen mutasyon M694V (%58,2) iken R202Q (%27,6) ve V726A (%18,2) diğer sık görülen mutasyonlardı. 277 AAA hastasının 36’sında (%13) eşlik eden sistemik bir hastalık saptanırken en sık Ankilozan spondilit (7 hasta) vardı. Sonuç: AAA ülkemizde sık görülen ve ayırıcı tanıda güçlük yaşanan bir hastalıktır. Otoinflamatuar bir hastalık olup çeşitli inflamatuar hastalıklar ve vaskülitler ile ilişkili olabilir. MEFV genindeki mutasyonlar olguların büyük bir çoğunluğunda tespit edilmektedir. Bu çalışmanın sonuçları MEFV gen mutasyonundaki heterojeniteyi ve bölgemizdeki hastaların geniş bir mutasyon çeşitliliğine sahip olduğunu göstermiştir.

Genetic Characteristics of Familial Mediterranean Fever and Its Relationship with Systemic Diseases

Objective: This study aims to analyze the genetic characteristics of patients with familial Mediterranean fever (FMF) and to evaluate the relationship between FMF and systemic diseases. Material and Method: In this study, data of 277 AAA patients who applied to the Internal Medicine and Physical Therapy outpatient clinics of Tokat Gaziosmanpaşa University between January 2015 and May 2018 were evaluated retrospectively. Gender, age, FMF symptoms, concomitant systemic diseases and mutation analyzes were recorded. Results: Of the 277 AAA patients included in the study, 176 (63.5%) were female and 101 (36.5%) were male. The mean age of the patients was 33,6±11,8 years. A total of 170 (61%) of the FMF patients had a mutation analysis. Of them, 161 (95%) patients had mutation. The most common detected mutation was M694V (58.2%), while R202Q (27.6%) and V726A (18.2%) were the other common mutations. In 36 of 277 AAA patients (13%), a concomitant systemic disease was found, while the most common was Ankylosing spondylitis (7 patients). Conclusion: FMF is a common disease in our country. It is an autoinflammatory disease and may be associated with various inflammatory diseases and vasculitis. Mutations in the MEFV gene are detected in the majority of cases. The results of this study supported the heterogeneity of MEFV gene mutation and showed that patients in our region had a wide variety of mutations.

PDF

___

1. Tunca M, Akar S, Hawkins PN et al. The significance of paired MEFV mutations in individuals without symptoms of familial Mediterranean fever. Eur J Hum Genet 2002; 10: 786-9.
2. A candidate gene for familial Mediterranean fever. Nat Genet 1997; 17: 25-31.
3. Erken E, Erken E. Ailesel akdeniz ateşinin patogenezi. Turkiye Klinikleri J Rheumatol-Special Topics 2017; 10: 8-12.
4. Ozen S, Karaaslan Y, Ozdemir O et al. Prevalence of juvenile chronic arthritis and familial Mediterranean fever in Turkey: a field study. J Rheumatol 1998; 25: 2445-9.
5. Üreyen S, Terzioğlu E. Ailevi akdeniz ateşi. Turkiye Klinikleri J Immun Allergy-Special Topics 2015; 8: 1-5.
6. Yigit S, Karakus N, Kurt SG, Ates O. Association of missense mutations of Mediterranean fever (MEFV) gene with multiple sclerosis in Turkish population. J Mol Neurosci 2013; 50: 275-9.
7. Ozen S. Mutations/polymorphisms in a monogenetic autoinflammatory disease may be susceptibility markers for certain rheumatic diseases: lessons from the bedside for the benchside. Clin Exp Rheumatol 2009; 27: 29-31.
8. 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: 553-5.
9. Tunca M, Akar S, Onen F et al. Familial mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine (Baltimore) 2005; 84: 1-11.
10. Abuhandan M, Kaya C, Güzelçiçek A. Ailevi Akdeniz Ateşi tanısı alan 186 olgunun klinik semptom ve MEFV geni mutasyonlarının incelenmesi. Dicle Tıp Dergisi 2015; 42: 61-5.
11. Karakayali A, Erten S, Akan S et al. Demographic, clinical and genetic features of the patients with familial mediterranean fever. J Clin Anal Med 2017; 8: 43221.
12. Manukyan G, Aminov R. Update on pyrin functions and mechanisms of familial mediterranean fever. Front Microbiol 2016; 7: 456.
13. Simsek I, Pay S, Pekel A, et al. Serum proinflammatory cytokines directing T helper 1 polarization in patients with familial Mediterranean fever. Rheumatol Int 2007; 27: 807-11.
14. Dalkılıç E, Coşkun BN. Ailevi akdeniz ateşi ve vaskülit. Turkiye Klinikleri J PM&R-Special Topics 2015; 8: 33-7.
15. Ozcakar ZB, Cakar N, Uncu N, Celikel BA, Yalcinkaya F. Familial mediterranean fever-associated diseases in children. QJM 2017; 110: 287-90.
16. Altıntaş A, Paşa S, Çil T, Ayyıldız O. Familial mediterranean fever accompanied by ankylosing spondylitis: case report. . Turkiye Klinikleri J Med Sci 2008; 28: 399-402.
17. Kasifoglu T, Calisir C, Cansu DU, 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: 41-6.
18. Cosan F, Ustek D, Oku B et al. Association of familial mediterranean fever-related MEFV variations with ankylosing spondylitis. Arthritis Rheum 2010; 62: 3232-6.
19. Akkoc N, Gul A. Familial mediterranean fever and seronegative arthritis. Curr Rheumatol Rep 2011; 13: 388-94.
20. Alpayci M, Bozan N, Erdem S, Gunes M, Erden M. The possible underlying pathophysiological mechanisms for development of multiple sclerosis in familial Mediterranean fever. Med Hypotheses 2012; 78: 717-20.
21. Michet CJ. Epidemiology of vasculitis. Rheum Dis Clin North Am 1990; 16: 261-8.
22. Bayram C, Demircin G, Erdogan O, Bulbul M, Caltik A, Akyuz SG. Prevalence of MEFV gene mutations and their clinical correlations in Turkish children with Henoch-Schonlein purpura. Acta Paediatr 2011; 100: 745-9.
23. Can E, Kilinc Yaprak Z, Hamilcikan S, Erol M, Bostan Gayret YOYO. MEFV gene mutations and clinical course in pediatric patients with HenochSchonlein purpura. Arch Argent Pediatr 2018; 116: e385-91.
24. Lebwohl B, Sanders DS, Green PHR. Coeliac disease. Lancet 2018; 391: 70-81.
25. Isikay S, Isikay N, Kocamaz H. The prevalence of celiac disease among patients with familial mediterranean fever. Arq Gastroenterol 2015; 52: 55-8.
26. Kuloglu Z, Ozcakar ZB, Kirsaclioglu C et al. Is there an association between familial mediterranean fever and celiac disease? Clin Rheumatol 2008; 27: 1135-9.
27. Devrimsel G, Beyazal MS, Turkyilmaz AK. Coexistence of systemic lupus erythematosus and familial mediterranean fever. Lupus 2015; 24: 343- 4.