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BACKGROUND Tumor necrosis factor (TNF) is a proinflammatory cytokine that plays a major role in the sepsis and multiple organ dysfunction secondary to major trauma. The purpose of this article was to research the clinical relevance of the TNF gene polymorphism in patients with major trauma. METHODS Three hundred six patients with major trauma were prospectively recruited. The TNF gene polymorphisms were genotyped using restriction fragment length polymorphism analysis. Plasma TNF-α levels were determined with enzyme-linked immunosorbent assay. Sepsis morbidity rate and multiple organ dysfunction scores were accessed. RESULTS The TNF-α/-308 polymorphism was shown to be well associated with increased capacity of peripheral leukocytes to produce TNF-α in response to ex vivo lipopolysaccharide stimulation in trauma patients at admission. Results from association study indicated that trauma patients carrying the TNF-α/-308/A allele were more likely complicated with sepsis. CONCLUSIONS The TNF-α/-308 polymorphism might be used as a biomarker for the assessment of outcome of trauma patients, but the TNF-β/252 gene polymorphism might not influence the development of complications in patients with major trauma.

Toll-like receptor 2 (TLR2) signaling plays a critical role in orchestrating the innate immune response and the development of sepsis and subsequent organ dysfunction after trauma. The objectives of this prospective study were to identify haplotype tag single-nucleotide polymorphisms (htSNPs) within the entire TLR2 gene and to investigate their clinical relevance in patients with major trauma. A total of 410 patients with major trauma were prospectively recruited. The htSNPs of the TLR2 gene was determined using HapMap database and linkage disequilibrium analysis. The htSNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. The whole peripheral blood samples obtained immediately after admission were stimulated with bacterial lipoprotein and then determined for production of tumor necrosis factor-α, interleukin 8, and interleukin 10. Sepsis morbidity rate and multiple organ dysfunction (MOD) scores were accessed. Three SNPs (rs1898830, rs3804099, and rs7656411) were identified as htSNPs for the TLR2 gene. All of them were shown to be high-frequency SNPs in this study cohort. Two of them (rs1898830 and rs3804099) and the haplotype ATT were significantly associated with cytokine production by peripheral blood leukocytes in response to bacterial lipoprotein stimulation. Only rs3804099, however, was significantly associated with higher sepsis morbidity rate and MOD scores in patients with major trauma. In addition, the patients with the haplotype ATT had lower sepsis morbidity rate than those without the haplotype ATT. Therefore, three SNPs might act as htSNPs for the entire TLR2 gene in the Chinese population. The rs3804099 and the haplotype ATT might be used as relevant risk estimates for the development of sepsis and MOD in patients with major trauma.