Genomic polymorphism within the TNF and IL-10 locus influences outcome of patients undergoing liver resection.

背景：胆道恶性肿瘤的大范围肝切除会导致全身炎症反应和败血症并发症，导致器官功能障碍。这种发病率的媒介是细胞因子、肿瘤坏死因子(TNF)-α和白介素2。肿瘤坏死因子和白介素10基因的基因组多态性可能与大手术后高水平的肿瘤坏死因子和白介素10水平及高发病率有关。患者和方法：我们评估了在择期肝手术患者中肿瘤坏死因子和白介素10基因双等位基因多态性与促炎和抗炎细胞因子释放及术后脓毒症并发症的关系。对100例未经选择的连续行肝切除的患者进行了肿瘤坏死因子基因分型、血浆肿瘤坏死因子-α、白介素10浓度和败血症并发症的研究。结果与53例TNFB1纯合子或杂合子患者相比，TNFB2纯合子患者血清中肿瘤坏死因子-α和白细胞介素6的峰值浓度明显升高。TNFB2纯合子患者术后败血症并发症和术后器官功能障碍的发生率较高。TNFB2等位基因纯合的患者可能会发展为增强的全身炎症反应，并增加心脏手术后心肺并发症的风险。IL-10基因与术后脓毒症并发症相关。结论肿瘤坏死因子和IL-10基因多态性与胆道恶性肿瘤肝切除术后脓毒症并发症和器官功能障碍的风险增加有关。

<Background> Major liver resection for biliary malignancy induces a systemic inflammatory response characterized and septic complications resulting in organ dysfunction. Mediators for this morbidity are the cytokines tumor necrosis factor (TNF)-alpha and interleukins. Genomic polymorphism within the TNF and IL10 genes may be associated with increased TNF-alpha and IL-10 levels and high morbidity following major surgery.<Patients and Methods> We assessed the relationship of biallelic polymorphisms of the TNF and IL-10 genes in patients undergoing elective liver surgery to release of proinflammatory and anti-inflammatory cytokines and postoperative septic complications. TNF genotypes, plasma concentrations of TNF-alpha, IL-10, and septic complications were studied in 100 unselected, consecutive patients undergoing liver resection. TNF and IL-10 genotypes were determined by the solid-phase minisequencing method.<Results>Patients homozygous for the TNFB2 allele displayed larger peak concentrations of TNF-alpha and interleukin-6 when compared with patients homozygous or heterozygous for TNFB1 (n = 53). The TNFB2 homozygotes had a higher incidence of postoperative septic complications, and postoperative organ dysfunction. Patients homozygous for the TNFB2 allele may develop an enhanced systemic inflammatory response with an increased risk of cardiopulmonary morbidity after cardiac surgery. IL-10 genotypes were also correlated with postoperative septic complications.<Conclusions> Gene polymorphism of tumor necrosis factor (TNF) and IL-10 were associated with an increased risk of developing postoperative septic complications and organ dysfunction in patients undergoing liver resection for biliary malignancy.