SAT0019 Tumor Necrosis Factor-α -308 A/G Gene Polymorphism in Children with Juvenile Idiopathic Arthritis: Relation To Disease Activity, Damage and Disability
Authors: I.I. El Gazzar, H.M. Fathi, T.A. Gheita, A.M. Nour El-Din, E. Abdel Rasheed, R.H. Bassyouni, S.A. Kenawy
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood and an important cause of disability<sup>1</sup>. Its cause remains unknown, but likely includes complex interactions between genes and environmental exposures resulting in dysregulation of the immune system<sup>2</sup>. TNF-α is a cytokine with an important role in inflammation and immune function<sup>3</sup>. 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 susceptibility<sup>4</sup> <h3>Objectives</h3> 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 <h3>Methods</h3> 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. <h3>Results</h3> 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&lt;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). <h3>Conclusions</h3> 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. <h3>References</h3> Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet. 2007;369(9563):767–78. Moncrieffe H, Prahalad S, Thompson SD. Genetics of juvenile idiopathic arthritis: new tools bring new approaches. Curr Opin Rheumatol. 2014;26(5):579–84. 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 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. <h3>Disclosure of Interest</h3> None declared