TNF-α -857 and -1031 polymorphisms predict good therapeutic response to TNF-α blockers in Chinese Han patients with ankylosing spondylitis

Pharmacogenomics. 2012 Oct;13(13):1459-67. doi: 10.2217/pgs.12.133.

Abstract

Aim: To evaluate whether polymorphisms at -857, -1031, -308 and -238 positions of the TNF-α gene influence response to TNF-α-blocker therapy in Chinese Han patients with ankylosing spondylitis.

Patients & methods: A total of 106 patients with ankylosing spondylitis were recruited and genotyped for -857, -1031, -308 and -238 TNF-α gene polymorphisms. In total, 32 received infliximab and 74 received a recombinant human TNF-α receptor II-IgG Fc fusion protein (rhTNFR-Fc). At the end of 12 weeks, patients were assessed using the Assessment of SpondyloArthritis International Society (ASAS) 20, 40, 50 and 70 criteria.

Results: Polymorphisms at -308 and -238 did not affect therapeutic response. The -857 C/C genotype (p = 0.0021) responded better to therapy. The -1031 T/T genotype (p = 0.0004) showed better outcome.

Conclusion: In Chinese Han ankylosing spondylitis patients, polymorphisms at the -308 and -238 positions of the TNF-α gene are unable to predict TNF-α-blocker response; however, -857 C/C and -1031 T/T genotypes have the ability to predict good response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / therapeutic use
  • Asian People / genetics
  • Base Sequence
  • Case-Control Studies
  • China
  • DNA Primers / genetics
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / therapeutic use
  • Infliximab
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Spondylitis, Ankylosing / genetics*
  • Spondylitis, Ankylosing / immunology
  • Spondylitis, Ankylosing / therapy*
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / genetics*
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • DNA Primers
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Etanercept