Tumor necrosis factor-[alpha] -308 A/G gene polymorphism in children with juvenile idiopathic arthritis: relation to disease activity, damage, and functional status

• Published in: Clinical rheumatology 2017-08, Vol.36 (8), p.1757
• Main Authors: El Gazzar, Iman I, Fathy, Hanan M, Gheita, Tamer A, Nour El-din, Abeer M, Rasheed, Enas Abdel, Bassyouni, Rasha H, Kenawy, Sanaa A
• Format: Article
• Language: English
• Subjects: Alleles; Arthritis; C-reactive protein; Children; Enzyme-linked immunosorbent assay; Gene frequency; Gene polymorphism; Joint diseases; Necrosis; Polymerase chain reaction; Serum levels; Single-nucleotide polymorphism; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 0770-3198; 1434-9949
• DOI: 10.1007/s10067-017-3719-1

The study aims to evaluate the clinical significance of serum levels of tumor necrosis factor alpha (TNF-[alpha]) and -308 A/G promoter polymorphism in juvenile idiopathic arthritis (JIA) patients and find any association to the subsets, clinical and laboratory features, disease activity, and damage as well as functional disability. 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) was assessed, and Childhood Health Assessment Questionnaire (CHAQ) measured the functional status. Serum TNF-[alpha] was assayed by ELISA and gene (-308) promoter polymorphism was determined by polymerase chain reaction. The 48 JIA children (mean age 11.5 ± 2.8 years) were 13 systemic, 17 oligoarticular, and 18 polyarticular onset. The serum TNF-[alpha] 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-[alpha] -308 GG alleles. The frequency of GG genotype tended to be higher in systemic onset compared to oligoarticular and polyarticular subtypes. The serum TNF-[alpha] 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). There is evidence of a possible influence of the -308 SNP promoter position on the production of TNF-[alpha], the severity of JIA which may consequently influence the response to anti-TNF-[alpha] treatment.