Higher LPS-stimulated TNF-alpha 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.
To investigate the effects of TNF-alpha -308, -238 promoter polymorphisms on TNF-alpha transcription in B27 positive Chinese patients with ankylosing spondylitis (AS). The possible relationship between polymorphisms, MHC antigens, and quantitative TNF-alpha mRNA expression were evaluated. Single nucleotide polymorphisms (SNPS) of TNF-alpha -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-alpha mRNA in peripheral blood mononuclear cells was performed with real time RT-PCR. The polymorphisms were correlated to quantitative TNF-alpha mRNA, and MHC antigens (determined by SSP method) in AS patients. The prevalence rate of both -308G/A and -238G/A TNF-alpha promoter polymorphisms in patients were not significantly different from those in normal subjects. However, a significant high LPS-stimulated TNF-alpha 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-alpha 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-alpha production. It confirms once again the importance and complexity of MHC related molecules in disease pathogenesis of AS.
Lu
Ming-Chi
MC
Department of Allergy, Immunology and Rheumatology, Dalin Tzu Chi General Hospital, No 2, Ming-Sheng Road, Dalin Town, Chiayi, Taiwan.
Yang
K L
KL
Tung
Chien-Hsueh
CH
Huang
Kuang-Yung
KY
Yu
Hui-Chun
HC
Liu
Su-Qin
SQ
Lai
Ning-Sheng
NS
D044466:Asian People / Q000235:genetics*; D002478:Cells, Cultured; D002681:China / Q000208:ethnology; D015870:Gene Expression / Q000187:drug effects; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D013624:Taiwan / Q000208:ethnology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
D006680:HLA Antigens; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha