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

TNF 和 IL-10 位点内的基因组多态性影响接受肝切除术的患者的预后。

• 批准号: 14571178
• 负责人: KIMURA Fumio
• 金额: $ 2.24万
• 依托单位: CHIBA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571178/
• 关键词: Genomic Polymorphism; tumor necrosis factor (TNF); interleukin-10 (IL-10); Organ dysfunction; Liver resection; Cytokine; Chemokine; 術後感染症

<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.

<Background>胆道恶性肿瘤的主要肝切除术诱导全身炎症反应和脓毒性并发症，导致器官功能障碍。这种发病率的介质是细胞因子肿瘤坏死因子（TNF）-α和白细胞介素。TNF和IL-10基因内的基因组多态性可能与TNF-α和IL-10水平升高以及大手术后的高发病率相关。<Patients and Methods>我们评估了择期肝脏手术患者TNF和IL-10基因双等位基因多态性与促炎和抗炎细胞因子释放和术后脓毒症并发症的关系。在100例接受肝切除术的连续患者中研究了TNF基因型、TNF-α、IL-10的血浆浓度和脓毒症并发症。TNF和IL-10基因型通过固相微测序法测定。<Results>与TNFB 1纯合子或杂合子患者（n = 53）相比，TNFB 2等位基因纯合子患者TNF-α和白细胞介素-6的峰值浓度更高。TNFB 2纯合子患者术后感染性并发症和术后器官功能障碍的发生率较高。TNFB 2等位基因纯合子患者在心脏手术后可能会发生增强的全身炎症反应，并增加心肺疾病的风险。IL-10基因型也与术后脓毒症并发症相关。<Conclusions>肿瘤坏死因子（TNF）和IL-10的基因多态性与胆道恶性肿瘤行肝切除术患者发生术后脓毒症并发症和器官功能障碍的风险增加相关。

项目成果

Kimura F, Itoh H, Ambiru S, Shimizu H, Togawa A, Yoshidome H, Ohtsuka M, Shimizu Y, Shimamura F, Katoh A, Nukui Y, Miyazaki M.: "Circulating heat shock protein 70 is associated with postoperative infection and organ dysfunction following liver resection."

Kimura F、Itoh H、Ambiru S、Shimizu H、Tokawa A、Yoshidome H、Ohtsuka M、Shimizu Y、Shimamura F、Katoh A、Nukui Y、Miyazaki M.：“循环热休克蛋白 70 与术后感染和器官相关

Kimura F, et al.: "Sepsis delays gastric emptying following pylorus-preserving pancreatoduoclenectomy."Hepato-Gastroenterology. 49. 585-588 (2002)

Kimura F 等人：“保留幽门的胰十二指肠切除术后脓毒症会延迟胃排空。”肝胃肠病学。

Kimura F, et al.: "Evaluation of total hepatic vascular exclusion and pringle maneuver in liver resection"Hepato-Gastroenterology. 49/43. 225-230 (2002)

Kimura F 等人：“肝脏切除术中全肝血管排除和普林格尔操作的评估”肝胃肠病学。

Kimura F, et al.: "Circulating heat-shock protein 70 is associated with postoperative infection and organ dysfunction following liver resection"American Journal of surgery. (In press). (2004)

Kimura F 等人：“循环热休克蛋白 70 与肝切除术后感染和器官功能障碍有关”《美国外科杂志》。

Kimura F, et al.: "Evaluation of total hepatic vascular exclusion and pringle maneuver in liver resection."Hepato-Gastroenterology. 49. 225-230 (2002)

Kimura F 等人：“肝切除术中全肝血管排除和普林格尔操作的评估。”肝胃肠病学。