Analysis of associations between polymorphisms within genes coding for tumour necrosis factor (TNF)-alpha and TNF receptors and responsiveness to TNF-alpha blockers in patients with rheumatoid arthritis.

Jerzy Swierkot, Katarzyna Bogunia-Kubik, Beata Nowak, Katarzyna Bialowas, Lucyna Korman, Katarzyna Gebura, Katarzyna Kolossa, Slawomir Jeka, Piotr Wiland

Joint, bone, spine : revue du rhumatisme 2015 Mar

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Despite the fact that therapy with TNF-α inhibitors constitutes a breakthrough in rheumatoid arthritis management, no improvement is still achieved in approximately 30% of cases. The aim of the study was to evaluate whether single nucleotide polymorphisms (SNPs) within the TNF-α and TNF receptor encoding genes affect the efficacy of therapy with TNF-α inhibitors in patients with RA. Five SNPs within the TNF-α and TNF receptor encoding genes (TNFA: G-308A, G-238A, C-857T; TNFR1A G36A; TNFR1B T676G) were determined in 280 RA patients who had been treated with TNF-α inhibitors for at least 6 months or they stop therapy because of adverse events. The association between the relative change in DAS28 and SNP genotypes was tested by linear regression. At week 24, low disease activity or remission was achieved by 45% of the patients. After 6 months remission of the disease or low disease activity were more frequently observed among patients homozygous for the TNFR1A 36A allele than among those who were GG homozygotes (52% vs. 34%, P=0.04). At week 24 DAS28 was significantly lower in the subgroup of patients homozygous for the TNFA-857T variant compared to the C allele carriers (P=0.045). The other polymorphisms were not found to be significantly associated with EULAR response at week 12 and 24 of the anti-TNF treatment. Homozygosity for the TNFR1A 36A allele and the TNFA-875T variant could act as a genetic factor associated with better response to anti-TNF treatment. Copyright © 2014 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Citation

Jerzy Swierkot, Katarzyna Bogunia-Kubik, Beata Nowak, Katarzyna Bialowas, Lucyna Korman, Katarzyna Gebura, Katarzyna Kolossa, Slawomir Jeka, Piotr Wiland. Analysis of associations between polymorphisms within genes coding for tumour necrosis factor (TNF)-alpha and TNF receptors and responsiveness to TNF-alpha blockers in patients with rheumatoid arthritis. Joint, bone, spine : revue du rhumatisme. 2015 Mar;82(2):94-9