The influence of a polymorphism at position -857 of the tumour necrosis factor alpha gene on clinical response to etanercept therapy in rheumatoid arthritis

Abstract

Objectives: We aimed to test whether polymorphisms in the etanercept target genes TNFA and LTA are associated with clinical responses to etanercept therapy in RA patients.

Methods: Clinical responses of 70 patients treated with etanercept were determined according to the ACR criteria. We genotyped 13 single-nucleotide polymorphisms (SNPs) within TNFA and LTA and tested whether they influenced the responses to 12 weeks of etanercept therapy. Univariate and multivariate analyses were performed to compare allele, genotype and haplotype distributions between responders and non-responders.

Results: Association of the -857C/T SNP at the TNFA promoter was marginally significant when patients were divided into responders and non-responders according to improvement criteria ACR20 or ACR70. When ACR70 responders (the best responders) were compared with ACR20 non-responders (the worst responders), however, the association was prominent [odds ratio (OR) = 12, 95% confidence interval (CI) = 1.4-105, P = 0.0077, P(corrected) = 0.054], as the frequency of the T allele was 5% in the ACR20 non-responders but 39% in the ACR70 responders. Moreover, the ratio of ACR70 responder number to ACR20 non-responder number among T-allele carriers was >10-fold higher than in the C-allele homozygotes (OR = 12, 95% CI = 1.2-120, P = 0.033).

Conclusions: RA patients with the T allele of TNFA -857C/T SNP respond better to etanercept therapy than homozygotes for the C allele, indicating that, when the results have been confirmed, this SNP could become a useful genetic marker for predicting responses.