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

被引:0
作者
Ming-Chi Lu
K. L. Yang
Chien-Hsueh Tung
Kuang-Yung Huang
Hui-Chun Yu
Su-Qin Liu
Ning-Sheng Lai
机构
[1] Dalin Tzu Chi General Hospital,Department of Allergy, Immunology and Rheumatology
[2] Hualien Tzu Chi General Hospital,Stem Cells Center
[3] Tzu Chi University,College of Medicine
来源
Rheumatology International | 2008年 / 29卷
关键词
Ankylosing spondylitis; MHC; TNF-α promoter; TNF-α mRNA;
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学科分类号
摘要
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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