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SAT0019 Tumor Necrosis Factor-α -308 A/G Gene Polymorphism in Children with Juvenile Idiopathic Arthritis: Relation To Disease Activity, Damage and Disability
  1. I.I. El Gazzar1,
  2. H.M. Fathi2,
  3. T.A. Gheita1,
  4. A.M. Nour El-Din3,
  5. E. Abdel Rasheed4,
  6. R.H. Bassyouni5,
  7. S.A. Kenawy6
  1. 1Rheumatology and Clinical Immunology, Faculty of Medicine, Cairo University, Cairo
  2. 2Rheumatology, Faculty of Medicine, Fayoum University, Fayoum
  3. 3Pediatrics
  4. 4Clinical Pathology, National Research Centre (NRC), Giza
  5. 5Medical Microbiology and Immunology, Faculty of Medicine, Fayoum University, Fayoum
  6. 6Clinical Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, Egypt


Background Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood and an important cause of disability1. Its cause remains unknown, but likely includes complex interactions between genes and environmental exposures resulting in dysregulation of the immune system2. TNF-α is a cytokine with an important role in inflammation and immune function3. Several single nucleotide polymorphisms (SNPs) have been identified within the region of the TNF-α gene but only very small minority have proven functional consequences and were associated with JIA susceptibility4

Objectives To evaluate the clinical significance of serum levels of tumor necrosis factor alpha (TNFα) and -308 A/G promoter polymorphism in JIA patients and find any association to the subsets, clinical and laboratory features, disease activity and damage as well as functional disability

Methods Forty-eight JIA children and 30 controls were included in the present study. Juvenile arthritis disease activity score in 27 joints (JADAS-27) was calculated, juvenile arthritis damage index (JADI) assessed and Childhood Health Assessment Questionnaire (CHAQ) to measure the functional status. Serum TNF-α was assayed by ELISA and gene (-308) promoter polymorphism determined by polymerase chain reaction.

Results The 48 JIA children (mean age: 11.5±2.8 years) were 13 systemic, 17 oligoarticular and 18 polyarticular onset. The serum TNF-α was significantly higher in patients (90.4±6.3 ng/ml) compared to control (3.5±2.6 ng/ml) (p<0.0001) with a tendency to be higher in the polyarticular subtype. All controls had TNF-α -308GG alleles. The frequency of GG genotype tended to be higher in systemic onset compared to oligoarticular and polyarticular subtypes. The serum TNF-α significantly correlated with JADAS-27 (r=0.32, p=0.03) and CHAQ (r=0.37, p=0.01) and negatively with the presence of GG alleles (r=-0.48, p=0.001). The GG alleles were significantly negatively associated with C-reactive protein (r=-0.32, p=0.03) with a tendency to negatively correlate with JADAS-27, CHAQ and JADI-extrarticular (r=-0.28, p=0.06; r=-0.25, p=0.09 and r=-0.25, p=0.09 respectively).

Conclusions There is evidence of a possible influence of the −308 SNP promoter position on the production of TNF-α, the severity of JIA which may consequently influence the response to anti-TNF-α treatment.

  1. Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet. 2007;369(9563):767–78.

  2. Moncrieffe H, Prahalad S, Thompson SD. Genetics of juvenile idiopathic arthritis: new tools bring new approaches. Curr Opin Rheumatol. 2014;26(5):579–84.

  3. van den Ham HJ, de Jager W, Bijlsma JW, Prakken BJ, de Boer RJ. Differential cytokine profiles in juvenile idiopathic arthritis subtypes revealed by cluster analysis. Rheumatology. 2009;48:899–905

  4. Scardapane A, Breda L, Lucantoni M, Chiarelli F. TNF-α polymorphisms in juvenile idiopathic arthritis: which potential clinical implications? Int J Rheumatol. 2012;2012:756291.

Disclosure of Interest None declared

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