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

Abstract

The objective of this study was to investigate the influence of TNF-α promoter alleles on clinical response to etanercept therapy in JIA. TNF-α 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-α 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.