2003 Fiscal Year Final Research Report Summary
Genomic polymorphism within the TNF and IL-10 locus influences outcome of patients undergoing liver resection.
| Project/Area Number |
14571178
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
KIMURA Fumio Chiba University, Graduate School of Medicine, Lecturer, 大学院・医学研究院, 講師 (70334208)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDOME Hiroyuki Chiba University, University Hospital, Assistant, 医学部附属病院, 助手 (10312935)
TOGAWA Akira Chiba University, University Hospital, Assistant, 大学院・医学研究院, 助手 (80334192)
MIYAZAKI Masaru Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (70166156)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Genomic Polymorphism / tumor necrosis factor (TNF) / interleukin-10 (IL-10) / Organ dysfunction / Liver resection |
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| Research Abstract |
<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.
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Research Products
(6 results)
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[Publications] 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."Am J Surg. (in press). (2003)
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