Rheumatology International

, Volume 33, Issue 7, pp 1675–1680 | Cite as

The association of TNFRSF1A gene and MEFV gene mutations with adult onset Still’s disease

  • Fulya Cosan
  • Zeliha Emrence
  • Gokhan Erbag
  • Hulya Azakli
  • Baris Yilmazer
  • Ayten Yazici
  • Sema Sirma Ekmekci
  • Neslihan Abaci
  • Duran Ustek
  • Ayse Cefle
Original Article


Adult onset Still’s disease (ASD) is a systemic inflammatory disorder of unknown etiology. ASD is characterized by fever with unknown etiology, rash, arthritis, and involvement of several organ systems. FMF and TRAPS are two important autoinflammatory diseases which characterized with recurrent inflammatory attacks. We aimed in this study to investigate the MEFV gene and TNFRSF1A gene variations in ASD. Twenty consecutive Turkish ASD patients (14 female and 6 male; mean age 38.45 ± 14; mean disease duration 3.3 ± 2.3; mean age of the disease onset 35.1 ± 14.4) and 103 healthy controls of Turkish origin were analyzed. All ASD patients were genotyped for the 4 MEFV mutations (M694V, E148Q, V726A, M680I) and TNFRSF1A gene exon 2–3 and exon 4–5 by using sequence analysis. The healthy controls are genotyped using PCR–RFLP method for intron 4 variation. The results of MEFV gene mutations screening show an increase in the MEFV mutation rate in ASD group, but it was not significantly different (p = 0.442, OR 1.64, 95 % CI 0.409–6.589). T–C polymorphism (rs1800692) was the only variation in the intron 4 of TNFRSF1A gene that we observed at the ASD patients. The frequency of TT genotype was 15 %, TC: 45 %, and CC: 40 % in ASD patients and the frequencies were 22, 41, and 37 % in healthy controls, respectively. When we analyzed the allele difference between both groups, there was no difference (p = 0.54, OR 1.24, 0.619–2.496–2.654). The variations in MEFV may have role in ASD pathogenesis. Our findings suggest that there is no significant association between ASD and TNFRSF1A variations.


Adult onset Still’s disease Familial Mediterranean fever TRAPS TNFRSF1A gene MEFV gene 



Ankylosing spondylitis


Adult onset Still’s disease


Cryopyrin-associated periodic syndrome


Confidence interval


Chronic recurrent multifocal osteomyelitis


Deficiency of the IL-1 receptor antagonist


Endoplasmic reticulum


Familial Mediterranean fever


Healthy control


Hyperimmunoglobulinemia D with periodic fever syndrome


Hereditary periodic fever syndromes


Inflammatory bowel disease




Mediterranean fever

NF-kappa B

Nuclear factor-kappa B


Odds ratio


Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome


Polymerase chain reaction


Rheumatoid arthritis


Restriction fraction length polymorphism


Tumor necrosing factor


TNF receptor-associated periodic syndrome


Tumor necrosing factor receptor superfamily 1A


Conflict of interest



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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Fulya Cosan
    • 1
    • 2
  • Zeliha Emrence
    • 2
  • Gokhan Erbag
    • 1
  • Hulya Azakli
    • 2
  • Baris Yilmazer
    • 1
  • Ayten Yazici
    • 1
  • Sema Sirma Ekmekci
    • 2
  • Neslihan Abaci
    • 2
  • Duran Ustek
    • 2
  • Ayse Cefle
    • 1
  1. 1.Division of Rheumatology, Department of Internal Medicine, Faculty of MedicineKocaeli UniversityKocaeliTurkey
  2. 2.Division of Genetics, Institute for Experimental Medical ResearchIstanbul UniversityIstanbulTurkey

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