Effects of a single nucleotide polymorphism on the expression of human tumor necrosis factor-alpha
Effects of a single nucleotide polymorphism on the expression of human tumor necrosis factor-alpha
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DOI：
10.1111/j.1365-3083.2006.01786.x
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发表时间：
2006-08-01
影响因子：
3.7
通讯作者：
Sun, S.
中科院分区：
文献类型：
--
作者：
Lv, K.;Chen, R.;Sun, S.
肿瘤坏死因子（TNF）-α在炎症中起重要作用，是一种促炎细胞因子，与自身免疫性疾病和感染性疾病的发病机制有关。近期的关联研究发现，TNF -α -857T等位基因与多种疾病相关。在此我们通过受两种等位基因TNF -α启动子控制的报告基因证明，在脂多糖刺激下，在RAW264.7细胞系中，次要等位基因 -857T比主要等位基因 -857C具有更强的转录激活作用。然而，在HeLa细胞系中结果并不一致。此外，为了对健康受试者的 -857C/C基因型和强直性脊柱炎（AS）患者的 -857C/T基因型之间的TNF -α合成进行定量分析，分别进行了定量逆转录 - 聚合酶链反应和酶联免疫吸附测定。两组在mRNA和蛋白质水平上均无显著差异。这些结果表明，这种多态性可能以组织特异性的方式对TNF -α的调节产生直接影响，并且除了TNF -α启动子中 -857处的多态性外，可能还有其他因素影响TNF -α的表达。
Tumor necrosis factor (TNF)-alpha plays a prominent role in inflammations and is a proinflammatory cytokine that has been implicated in the pathogenesis of autoimmune and infectious diseases. Recent association studies have found that the TNF-alpha-857T allele was associated with several disorders. Here we demonstrate, with reporter genes under the control of the two allelic TNF-alpha promoters, that the minor allele -857T is a much stronger transcriptional activator than the major allele -857C in RAW264.7 cell line in response to lipopolysaccharide stimulation. However, the result was not consistent in HeLa cell line. Furthermore, for the quantitative analysis of TNF-alpha synthesis between the -857C/C genotype from healthy subjects and the -857C/T genotype from AS patients, the quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were performed separately. There was no significant difference between the two groups at the level of mRNA and protein. These results show that this polymorphism may have a direct effect on TNF-alpha regulation in a tissue-specific manner, and apart from the polymorphism at -857 in the TNF-alpha promoter, there may be other factors affecting the expression of TNF-alpha.