Rheumatology International

, Volume 33, Issue 7, pp 1675–1680

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

Authors

    • Division of Rheumatology, Department of Internal Medicine, Faculty of MedicineKocaeli University
    • Division of Genetics, Institute for Experimental Medical ResearchIstanbul University
  • Zeliha Emrence
    • Division of Genetics, Institute for Experimental Medical ResearchIstanbul University
  • Gokhan Erbag
    • Division of Rheumatology, Department of Internal Medicine, Faculty of MedicineKocaeli University
  • Hulya Azakli
    • Division of Genetics, Institute for Experimental Medical ResearchIstanbul University
  • Baris Yilmazer
    • Division of Rheumatology, Department of Internal Medicine, Faculty of MedicineKocaeli University
  • Ayten Yazici
    • Division of Rheumatology, Department of Internal Medicine, Faculty of MedicineKocaeli University
  • Sema Sirma Ekmekci
    • Division of Genetics, Institute for Experimental Medical ResearchIstanbul University
  • Neslihan Abaci
    • Division of Genetics, Institute for Experimental Medical ResearchIstanbul University
  • Duran Ustek
    • Division of Genetics, Institute for Experimental Medical ResearchIstanbul University
  • Ayse Cefle
    • Division of Rheumatology, Department of Internal Medicine, Faculty of MedicineKocaeli University
Original Article

DOI: 10.1007/s00296-012-2609-8

Cite this article as:
Cosan, F., Emrence, Z., Erbag, G. et al. Rheumatol Int (2013) 33: 1675. doi:10.1007/s00296-012-2609-8

Abstract

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.

Keywords

Adult onset Still’s diseaseFamilial Mediterranean feverTRAPSTNFRSF1A geneMEFV gene

Abbreviations

AS

Ankylosing spondylitis

ASD

Adult onset Still’s disease

CAPS

Cryopyrin-associated periodic syndrome

CI

Confidence interval

CRMO

Chronic recurrent multifocal osteomyelitis

DIRA

Deficiency of the IL-1 receptor antagonist

ER

Endoplasmic reticulum

FMF

Familial Mediterranean fever

HC

Healthy control

HIDS

Hyperimmunoglobulinemia D with periodic fever syndrome

HPFS

Hereditary periodic fever syndromes

IBD

Inflammatory bowel disease

IL

Interleukin

MEFV

Mediterranean fever

NF-kappa B

Nuclear factor-kappa B

OR

Odds ratio

PAPA

Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome

PCR

Polymerase chain reaction

RA

Rheumatoid arthritis

RFLP

Restriction fraction length polymorphism

TNF

Tumor necrosing factor

TRAPS

TNF receptor-associated periodic syndrome

TNFRSF1A

Tumor necrosing factor receptor superfamily 1A

Copyright information

© Springer-Verlag Berlin Heidelberg 2012