Genetic contribution of suppressor of cytokine signalling polymorphisms to the susceptibility to infection after traumatic injury

Autor:	Ling Zeng, Wei Gu, An Qiang Zhang, Lian-yang Zhang, Dalin Wen, Xiao Wang, Jianxin Jiang, J Hao, Ding-yuan Du, Hongxiang Lu
Rok vydání:	2018
Předmět:	Adult Male 0301 basic medicine Adolescent Multiple Organ Failure Immunology Suppressor of Cytokine Signaling Proteins Single-nucleotide polymorphism Polymorphism Single Nucleotide Suppressor of cytokine signalling Sepsis Young Adult 03 medical and health sciences 0302 clinical medicine Genotype medicine Humans Immunology and Allergy Genetic Predisposition to Disease Prospective Studies Allele Promoter Regions Genetic CISH Aged Tumor Necrosis Factor-alpha business.industry Interleukin Original Articles Middle Aged medicine.disease Interleukin-10 030104 developmental biology 030220 oncology & carcinogenesis Wounds and Injuries Female Multiple organ dysfunction syndrome business
Zdroj:	Clinical and Experimental Immunology. 194:93-102
ISSN:	1365-2249 0009-9104
DOI:	10.1111/cei.13160
Popis:	Summary 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.
Databáze:	OpenAIRE
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