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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

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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.

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Authors and Affiliations

  1. Department of Allergy, Immunology and Rheumatology, Dalin Tzu Chi General Hospital, No 2, Ming-Sheng Road, Dalin Town, Chiayi, Taiwan

    Ming-Chi Lu, Chien-Hsueh Tung, Kuang-Yung Huang, Hui-Chun Yu, Su-Qin Liu & Ning-Sheng Lai

  2. Stem Cells Center, Hualien Tzu Chi General Hospital, Hualien, Taiwan

    K. L. Yang

  3. College of Medicine, Tzu Chi University, Hualien, Taiwan

    Ning-Sheng Lai

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  1. Ming-Chi Lu
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  2. K. L. Yang
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  4. Kuang-Yung Huang
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Correspondence to Ning-Sheng Lai.

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Lu, MC., Yang, K.L., Tung, CH. et al. 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. Rheumatol Int 29, 189–195 (2008). https://doi.org/10.1007/s00296-008-0671-z

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