Tumor Necrosis Factor-alpha-308 a/G Gene Polymorphism in Children with Juvenile Idiopathic Arthritis: Relation to Disease Activity, Damage and Disability

Background Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood and an important cause of disability 1 . Its cause remains unknown, but likely includes complex interactions between genes and environmental exposures resulting in dysregulation of the immune system 2 . TNF-α is a cytokine with an important role in inflammation and immune function 3 . 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 4 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 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. References 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. Disclosure of Interest None declared