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首页> 外文期刊>Rheumatology international. >Higher LPS-stimulated TNF-alpha mRNA levels in peripheral blood mononuclear cells from Chinese ankylosing spondylitis patients with -308(G/A) polymorphism in promoter region of tumor necrosis factor: association with distinct A33/B58/Cw10 haplotypes
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Higher LPS-stimulated TNF-alpha mRNA levels in peripheral blood mononuclear cells from Chinese ankylosing spondylitis patients with -308(G/A) polymorphism in promoter region of tumor necrosis factor: association with distinct A33/B58/Cw10 haplotypes

机译：在肿瘤坏死因子启动子区域具有-308（G / A）多态性的中国强直性脊柱炎患者外周血单核细胞中LPS刺激的TNF-αmRNA水平更高：与不同的A33 / B58 / Cw10单倍型相关

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摘要

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 -308(G/A) and -238(G/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 -308(G/A) polymorphism (TNF2) as compared to those in -308(G/G) genotype (TNF1). Furthermore, -308(G/A) polymorphism in patients was found to be tightly associated with distinct haplotypes of A33/B58/Cw10 [12 out of 14 -308(G/A) patients (85.7%) versus none in 53 -308(G/G) patients], independent of B27 antigen. HLA-A33-B58-Cw10 haplotypes associated TNF-alpha promoter -308(G/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.
机译：研究TNF-α-308，-238启动子多态性对B27阳性中国强直性脊柱炎（AS）患者TNF-α转录的影响。评价了多态性，MHC抗原和定量TNF-αmRNA表达之间的可能关系。通过PCR-扩增难治性突变系统方法（PCR-ARMS）对67例B27阳性AS患者和60例中国HLA-B27阳性健康对照者进行了TNF-α-308和-238的单核苷酸多态性（SNPS）。用实时RT-PCR对外周血单核细胞中TNF-αmRNA进行定量测定。该多态性与AS患者中定量的TNF-αmRNA和MHC抗原（通过SSP法测定）相关。患者中-308（G / A）和-238（G / A）TNF-alpha启动子多态性的患病率与正常受试者无明显差异。然而，与-308（G / G）基因型（TNF1）相比，在具有启动子-308（G / A）多态性（TNF2）的患者的外周血单核细胞中发现了显着高的LPS刺激的TNF-αmRNA表达。 ）。此外，发现患者的-308（G / A）多态性与A33 / B58 / Cw10的不同单倍型紧密相关[14 -308（G / A）患者中有12个（85.7％），而在53 -308中没有一个（G / G）患者]，独立于B27抗原。 HLA-A33-B58-Cw10单倍型相关的TNF-α启动子-308（G / A）多态性可能在中国人群AS的发病机制中起重要作用，部分与较高的TNF-α产生的驱动力有关。它再次证实了MHC相关分子在AS疾病发病机理中的重要性和复杂性。

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