Vol.18 No.5

Original Article

Tristetraprolin (TTP) gene polymorphisms in patients with rheumatoid arthritis and healthy individuals

Authors

Takeshi Suzuki1 , Akito Tsutsumi1 , Hiroyuki Suzuki2 , Eiji Suzuki1 , Makoto Sugihara1 , Yoshifumi Muraki1 , Taichi Hayashi1 , Yusuke Chino1 , Daisuke Goto1 , Isao Matsumoto1 , Satoshi Ito1 , Keiji Miyazawa3, Takayuki Sumida1

  • Division of Clinical Immunology, Major of Advanced Biomedical Applications, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Ibaraki, Japan
  • Department of Experimental Pathology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
  • Central Research Laboratories, Kissei Pharmaceutical Company, Azumino, Japan
Received:

21 January 2008

Accepted:

16 April 2008

Published online:

7 June 2008

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Abstract

Tristetraprolin (TTP) is an intracellular protein that modulates the production of cytokines, including TNFα, by binding to and destabilizing the mRNAs of these cytokines. Therefore, differences in TTP gene expression may affect the severity of inflammatory diseases, such as rheumatoid arthritis (RA). Wesearched for polymorphisms in the human TTP gene and for this purpose, we sequenced the entire TTP gene in 20 Japanese individuals (ten with RA and ten healthy volunteers) and found one single nucleotide polymorphism (SNP) in the promoter region. We analyzed this SNP (A/G) by restriction fragment length polymorphism method in 155 RA patients and 100 control subjects. While the frequency of A allele in this SNP was similar in RA patients (74.5%) and controls (76.0%), the disease duration in RA patients with genotype GG was shorter than that of patients with genotypes AA/AG and RA patients with genotype GG had a higher probability of being treated with infliximab. We studied the difference in promoter activity between the two alleles by luciferase assay and found that the promoter activity of TTP promoter region with allele A was around two-fold higher than that with allele G. We conclude that this SNP in the promoter region of the TTP gene mildly affects promoter activity, and thus, may influence the disease activity of inflammatory disorders including RA.

Key words

Tristetraprolin - ZFP36 - Single nucleotide polymorphism - TNF-α - Rheumatoid arthritis