Evaluation of Effects of TNF- α Promoter Polymorphism on
the Therapeutic Response of Enbrel and Humira in
Patients with Rheumatoid Arthritis
Adviser: Dr. Hsien-Bin Huang Speaker: Ting-Yu Lin
Date: 2012.06.08
Abstract
Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation
of the joints. RA can also cause inflammation of the tissue around the joints, as well
as in other organs of the body. The joint inflammation of RA causes swelling, pain,
stiffness, and redness in the joints. The chronic inflammation leads to the destruction
of the cartilage, bone, and ligaments, causing deformity of the joints.
Tumor necrosis factor-α (TNF-α), a macrophage-derived cytokine, has been suggested
to play a major role in the pathogenesis of RA. Factors related to TNF-α regulation,
including genotypes of TNF-α gene, might play a crucial role in tissue inflammation.
Many single nucleotide polymorphisms (SNPS) within the TNF- gene and in its
promoter region have been identified.
TNF-α antagonist has emerged as an effective therapeutic agent in the treatment of
RA, including etanercept, infliximab and adalimumab. Recent studies had shown that
most of RA patients (around 70% patients) responded well to biological agents.
However, part of RA patients (around 20-30%) showed a late failure in continuous
injections and needed to be changed to other biological agents. The determinants
associated with therapeutic responses remained unknown. Thus, I would like to
examine whether or not the TNF- promoter polymorphism is associated with
responsiveness to anti-TNF- therapy in RA patients.
Our result found that there was a significant association between -857 genotype and
anti-TNF therapy efficiency of 61patients treated with Enbrel. The odd ratios (ORs)
and 95% confidence intervals (CI) for C/T versus C/C genotype of TNF -857 C/T
polymorphism were 0.111 (0.013–0.92). There was also a significant association
between -857 genotype and anti-TNF therapy efficiency of 27 patients treated with
Humira. Furthermore, there was no association between TNF SNP and therapy
efficiency of patients treated with Rituximab.