Genetic contribution of suppressor of cytokine signalling polymorphisms to the susceptibility to infection after traumatic injury
Genetic contribution of suppressor of cytokine signalling polymorphisms to the susceptibility to infection after traumatic injury
复制标题
细胞因子信号多态性抑制因子对创伤后感染易感性的遗传贡献
DOI：
10.1111/cei.13160
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发表时间：
2018-10-01
影响因子：
4.6
通讯作者：
Jiang, J.
中科院分区：
文献类型：
--
作者：
Zhang, A.;Gu, W.;Jiang, J.
细胞因子信号转导抑制因子（SOCS）蛋白是许多信号转导途径中的重要负调控因子，与感染性疾病的发病机制密切相关。本研究的目的是揭示SOCS基因内常见多态性与创伤后感染结局的可能关联。共招募了1087例创伤患者（重庆队列806和云南队列281），并随访了感染结局，如脓毒症和多器官功能障碍综合征（MODS）。通过焦磷酸测序筛选了12个选定的单核苷酸多态性（SNP），以确定其基因型及其与感染并发症的相关性。在12个选择的SNP中，尽管单独或联合分析SNP，但仅发现细胞因子诱导型Src同源（SH 2）结构域蛋白（CISH）启动子rs 414171多态性与两个队列中脓毒症的发生率和MOD评分在统计学上一致相关。此外，具有T等位基因的患者具有显著较低的CISH表达和较低的肿瘤坏死因子（TNF）-α产生，但较高的白细胞介素（IL）-10产生。荧光素酶检测证实rs 414171位点A→T变异对CISH基因的转录活性有明显的抑制作用。CISH rs 414171多态性与创伤患者脓毒症和MODS的易感性显著相关，可能成为一种新的生物标志物，用于指示危重创伤患者感染结局的风险。
Suppressor of cytokine signalling (SOCS) proteins are crucial negative regulators in many signalling pathways and are implicated in the pathogenesis of infectious diseases. The purpose of this study was to uncover possible associations of common polymorphisms within SOCS genes with infectious outcomes after traumatic injury. A total of 1087 trauma patients (Chongqing cohort 806 and Yunnan cohort 281) were recruited and followed‐up for the development of infectious outcomes, such as sepsis and multiple organ dysfunction syndrome (MODS). Twelve selected single nucleotide polymorphisms (SNPs) were screened by pyrosequencing to determine their genotypes and associations with infectious complications. Among the 12 selected SNPs, only the cytokine‐inducible Src homology (SH2) domain protein (CISH) promoter rs414171 polymorphism was found consistently to be associated statistically with the incidence of sepsis and MOD score in the two cohorts, despite analysing the SNPs independently or in combination. Further, patients with a T allele had significantly lower CISH expression and lower production of tumour necrosis factor (TNF)‐α, but higher production of interleukin (IL)‐10. Luciferase assay confirmed that the A→T variant in the rs414171 polymorphism inhibited the transcriptional activities of the CISH gene significantly. The CISH rs414171 polymorphism is associated significantly with susceptibility to sepsis and MODS in traumatic patients, which might prove to be a novel biomarker for indicating risk of infectious outcomes in critically injured patients.