TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study
TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study
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DOI：
10.1038/sj.gene.6364136
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发表时间：
2004-12-01
影响因子：
5
通讯作者：
Hinds, CJ
中科院分区：
文献类型：
--
作者：
Gordon, AC;Lagan, AL;Hinds, CJ
肿瘤坏死因子是脓毒症时产生的一种重要的促炎细胞因子。检测个体肿瘤坏死因子单核苷酸多态与脓毒症的相关性的研究产生了相互矛盾的结果。本研究调查了肿瘤坏死因子基因和两个受体基因TNFRSF1A和TNFRSF1B的常见多态是否影响编码蛋白的循环水平，以及这些基因的个体多态或扩展单倍型是否与成人严重脓毒症或感染性休克患者的易感性、疾病严重程度或预后有关。来自英国和澳大利亚的8个重症监护室(ICU)共招募了213名高加索患者。ICU死亡者血浆肿瘤坏死因子水平(P=0.005.0 2)、sTNFRSF1A水平(P=0.0 1)和sTNFRSF1B水平(P=0.0 1)均显著高于存活者。可溶性受体水平升高与器官功能障碍(SOFA评分增加)呈正相关(sTNFRSF1AR=0.51，P
Tumour necrosis factor (TNF) is an important pro-inflammatory cytokine produced in sepsis. Studies examining the association of individual TNF single nucleotide polymorphisms with sepsis have produced conflicting results. This study investigated whether common polymorphisms of the TNF locus and the two receptor genes, TNFRSF1A and TNFRSF1B, influence circulating levels of encoded proteins, and whether individual polymorphisms or extended haplotypes of these genes are associated with susceptibility, severity of illness or outcome in adult patients with severe sepsis or septic shock. A total of 213 Caucasian patients were recruited from eight intensive care units (ICU) in the UK and Australia. Plasma levels of TNF ( P = 0.02), sTNFRSF1A ( P = 0.005) and sTNFRSF1B ( P = 0.01) were significantly higher in those who died on ICU compared to those who survived. There was a positive correlation between increasing soluble receptor levels and organ dysfunction ( increasing SOFA score) ( sTNFRSF1A R = 0.51, P