Tumour necrosis factor alpha promoter polymorphisms and etanercept therapy in juvenile idiopathic arthritis.

The objective of this study was to investigate the influence of TNF-alpha promoter alleles on clinical response to etanercept therapy in JIA. TNF-alpha promoter polymorphisms at positions -163, -238, -244, -308, -376 were determined in 137 JIA patients treated with etanercept for at least 3 months. A PCR fragment of about 500 bp of the TNF gene promoter was amplified. Polymorphisms were detected by a single sequencing procedure. Patients with the genotype -308GG achieved an ACR-JRA 30 response at month 6 more frequently than patients with the genotype -308GA or AA. This was already notable at month 3 of therapy. This difference in the total patient group is attributable to the JIA subgroup with rheumatoid factor negative polyarthritis. In this subgroup, patients with the -308GG genotype achieved an ACR-JRA 30 response more frequently than those with the -308GA or AA genotype (84 vs. 33% at months three, P < 0.01, 93 vs. 67% at months six, P < 0.05). There was no influence of the -238 TNF-alpha promoter alleles on clinical response. The rare alleles at position -376 or at positions -163 and -244 were too infrequent. There is an association between TNF gene promoter polymorphisms and response to etanercept in rheumatoid factor negative polyarticular JIA.