Clinical relevance of 13 cytokine gene polymorphisms in Chinese major trauma patients

Clinical relevance of 13 cytokine gene polymorphisms in Chinese major trauma patients
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DOI:
10.1007/s00134-010-1797-5
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发表时间:
2010-07-01
影响因子:
38.9
通讯作者:
Jiang, Jian-xin
Jiang, Jian-xin
中科院分区:
医学1区
文献类型:
--
作者:
Gu, Wei;Zeng, Ling;Jiang, Jian-xin

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为探讨13种常见的细胞因子基因单核苷酸多态性(SNPs)与严重创伤患者的临床相关性,在已有的功能或关联研究基础上,选取9个关键细胞因子基因的13个SNPs,对308例严重创伤患者进行关联研究。等位基因特异性寡核苷酸阵列的开发和使用的基因型308例严重创伤患者。通过观察创伤患者细胞因子的产生和预后来评估13个SNP的临床相关性。(IL-1 β)/-1470,IL-1 β/-511,IL-1 β/-31,IL-4/-589,IL-6/-572,IL-8/-251,IL-10/-819,和肿瘤坏死因子α(TNF α)/-308]与外周血白细胞响应脂多糖(LPS)的相应离体细胞因子产生相关入院时的刺激,或在严重创伤患者中发生脓毒症或器官功能障碍的风险。IL-1 β/-1470、IL-1 β/-511、IL-1 β/-31、IL-4/-589、IL-6/-572、IL-8/-251、IL-10/-819、和TNF α/-308是严重创伤患者发生脓毒症和器官功能障碍的易感基因座。
To determine the clinical relevance of 13 reported common single-nucleotide polymorphisms (SNPs) of cytokine genes in patients with major trauma.Thirteen SNPs in nine key cytokine genes were selected for association study in 308 patients with major trauma on the basis of previous functional or association data. An allele-specific oligonucleotide array was developed and used to genotype 308 patients with major trauma. The clinical relevance of the 13 SNPs was assessed by observation of cytokine production and outcome of trauma patients.Results from the allele-specific oligonucleotide array indicated that 8 [interleukin-1 beta (IL-1 beta)/-1470, IL-1 beta/-511, IL-1 beta/-31, IL-4/-589, IL-6/-572, IL-8/-251, IL-10/-819, and tumor necrosis factor alpha (TNF alpha)/-308] out of the 13 SNPs were associated with respective ex vivo cytokine production by peripheral leukocytes in response to lipopolysaccharide (LPS) stimulation at admission, or risk of development of sepsis or organ dysfunction in major trauma patients. Patients with more than four risk alleles of the eight SNPs had more than 50% sepsis morbidity and more severe organ dysfunction.Polymorphisms of IL-1 beta/-1470, IL-1 beta/-511, IL-1 beta/-31, IL-4/-589, IL-6/-572, IL-8/-251, IL-10/-819, and TNF alpha/-308 are susceptibility loci for the development of sepsis and organ dysfunction in major trauma patients.