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首页> 外文期刊>Rheumatology International >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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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

机译：在肿瘤坏死因子启动子区域中具有-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-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.
机译：为了研究TNF-α-308，-238启动子多态性对中国B27阳性强直性脊柱炎（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定量测定外周血单个核细胞中TNF-α的mRNA。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。患者的-308 G / A 和-238 G / A TNF-α启动子多态性的患病率与正常人无明显差异。但是，与-308 G / A 多态性（TNF2）启动子患者相比，在-308 G / A 多态性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。 G / G 基因型（TNF1）。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 患者中的12个（85.7％）vs. 53 –308 G / G 患者中无一]，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发病中起重要作用，部分与较高TNF的驱动力有关-α生产。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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