State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Daping, Chongqing, 400042, China.
Intensive Care Med. 2010 Jul;36(7):1261-5. doi: 10.1007/s00134-010-1797-5. Epub 2010 Mar 9.
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-1beta (IL-1beta)/-1470, IL-1beta/-511, IL-1beta/-31, IL-4/-589, IL-6/-572, IL-8/-251, IL-10/-819, and tumor necrosis factor alpha (TNFalpha)/-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-1beta/-1470, IL-1beta/-511, IL-1beta/-31, IL-4/-589, IL-6/-572, IL-8/-251, IL-10/-819, and TNFalpha/-308 are susceptibility loci for the development of sepsis and organ dysfunction in major trauma patients.
确定 13 个已报道的细胞因子基因常见单核苷酸多态性（SNP）在重大创伤患者中的临床相关性。
根据先前的功能或关联数据，选择了 9 个关键细胞因子基因中的 13 个 SNP，用于对 308 例重大创伤患者进行关联研究。开发了一种等位基因特异性寡核苷酸阵列，并用于对 308 例重大创伤患者进行基因分型。通过观察细胞因子产生和创伤患者的结果来评估 13 个 SNP 的临床相关性。
等位基因特异性寡核苷酸阵列的结果表明，在入院时对外周白细胞进行脂多糖（LPS）刺激后的细胞因子产生或重大创伤患者发生败血症或器官功能障碍的风险，13 个 SNP 中有 8 个（IL-1beta/-1470、IL-1beta/-511、IL-1beta/-31、IL-4/-589、IL-6/-572、IL-8/-251、IL-10/-819 和肿瘤坏死因子 alpha（TNFalpha）/-308）与各自相关。这 8 个 SNP 中携带 8 个以上风险等位基因的患者，其败血症发病率超过 50%，器官功能障碍更严重。
IL-1beta/-1470、IL-1beta/-511、IL-1beta/-31、IL-4/-589、IL-6/-572、IL-8/-251、IL-10/-819 和 TNFalpha/-308 的多态性是重大创伤患者发生败血症和器官功能障碍的易感基因座。
