Rheumatology International

, 29:189

Higher LPS-stimulated TNF-α mRNA levels in peripheral blood mononuclear cells from Chinese ankylosing spondylitis patients with −308G/A polymorphism in promoter region of tumor necrosis factor: association with distinct A33/B58/Cw10 haplotypes

  • Ming-Chi Lu
  • K. L. Yang
  • Chien-Hsueh Tung
  • Kuang-Yung Huang
  • Hui-Chun Yu
  • Su-Qin Liu
  • Ning-Sheng Lai
Original Article

DOI: 10.1007/s00296-008-0671-z

Cite this article as:
Lu, MC., Yang, K.L., Tung, CH. et al. Rheumatol Int (2008) 29: 189. doi:10.1007/s00296-008-0671-z

Abstract

To investigate the effects of TNF-α −308, −238 promoter polymorphisms on TNF-α transcription in B27 positive Chinese patients with ankylosing spondylitis (AS). The possible relationship between polymorphisms, MHC antigens, and quantitative TNF-α mRNA expression were evaluated. Single nucleotide polymorphisms (SNPS) of TNF-α −308 and −238 were performed by PCR-amplification refractory mutation system method (PCR-ARMS) in sixty-seven B27-positive AS patients and 60 HLA-B27 positive healthy controls in Chinese. Quantitative measurement of TNF-α mRNA in peripheral blood mononuclear cells was performed with real time RT-PCR. The polymorphisms were correlated to quantitative TNF-α mRNA, and MHC antigens (determined by SSP method) in AS patients. The prevalence rate of both −308G/A and −238G/A TNF-α promoter polymorphisms in patients were not significantly different from those in normal subjects. However, a significant high LPS-stimulated TNF-α mRNA expression was found in peripheral blood mononuclear cells from patients with promoter −308G/A polymorphism (TNF2) as compared to those in −308G/G genotype (TNF1). Furthermore, −308G/A polymorphism in patients was found to be tightly associated with distinct haplotypes of A33/B58/Cw10 [12 out of 14 –308G/A patients (85.7%) versus none in 53 –308G/G patients], independent of B27 antigen. HLA-A33-B58-Cw10 haplotypes associated TNF-α promoter −308G/A polymorphism might play an important role in disease pathogenesis of AS in Chinese population, partially related to a driving force of a higher TNF-α production. It confirms once again the importance and complexity of MHC related molecules in disease pathogenesis of AS.

Keywords

Ankylosing spondylitis MHC TNF-α promoter TNF-α mRNA 

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Ming-Chi Lu
    • 1
  • K. L. Yang
    • 2
  • Chien-Hsueh Tung
    • 1
  • Kuang-Yung Huang
    • 1
  • Hui-Chun Yu
    • 1
  • Su-Qin Liu
    • 1
  • Ning-Sheng Lai
    • 1
    • 3
  1. 1.Department of Allergy, Immunology and RheumatologyDalin Tzu Chi General HospitalChiayiTaiwan
  2. 2.Stem Cells CenterHualien Tzu Chi General HospitalHualienTaiwan
  3. 3.College of MedicineTzu Chi UniversityHualienTaiwan