title: Tumor necrosis factor-α -863 C/A promoter polymorphism affects the inflammatory response after cardiac surgery.
abstract: OBJECTIVE
  Cardiac surgery using cardiopulmonary bypass (CPB) initiates an inflammatory response that shows a wide inter-individual range and determines postoperative morbidity. Previous research suggests that genetic diversity contributes to individual susceptibility to perioperative trauma and stress. Nevertheless, the genetic triggering of the tumor necrosis factor-alpha (TNF-α) release remains unclear. We tested two genetic single-nucleotide polymorphisms (SNPs) from the promoter region of the TNF-α gene for associations with perioperative TNF-α level after CPB.
  
  
  METHODS
  We prospectively included 122 patients, who underwent elective coronary artery bypass grafting (CABG). Patients were genotyped for TNF-α -863 C/A (rs1800630) and TNF-α -308 G/A (rs1800629). Plasma level of TNF-α was obtained preoperatively, at the end of CPB, 6h postoperatively, and on the first postoperative day (POD).
  
  
  RESULTS
  Demographic characteristics and operative data revealed no significant differences between the different genotypes. Multiple linear regression analyses revealed significant associations for the TNF-α 863 C/A polymorphism: the major -863 CC variant was associated with higher TNF-α level preoperatively (p = 0.003), after CPB (p = 0.005), and 6h postoperatively (p = 0.010), independently from CPB time, left ventricle (LV) function and age. Contrarily, the AA allele had lower TNF-α level preoperatively (p = 0.008), after surgery (p = 0.024) and 6h postoperatively (p = 0.001). For the TNF-α 308 G/A polymorphism, only few significant associations could be observed: -308 GG carriers were associated with lower TNF-α level immediately after CPB (p = 0.020), whereas 308 AA carriers were significantly associated with elevated TNF-α level preoperatively (p = 0.032) and immediately after CPB (p = 0.05). No heterozygote variant of both SNPs revealed any significant associations with perioperative TNF-α level.
  
  
  CONCLUSIONS
  The current study suggests that the major -863 CC variant determines elevated TNF-α level preoperatively and throughout the postoperative course after CPB.
authors: Klinik fuer Herz- und Gefaesschirurgie, Deutsches Herzzentrum Muenchen, Technische Universitaet Muenchen, Lazarettstr 36, D-80636 Munich, Germany. johannesfboehm@googlemail.com
authors: Johannes
authors: J
authors: Boehm
authors: Katharina
authors: K
authors: Hauner
authors: Joachim
authors: J
authors: Grammer
authors: Wulf
authors: W
authors: Dietrich
authors: Stefan
authors: S
authors: Wagenpfeil
authors: Siegmund
authors: S
authors: Braun
authors: Rüdiger
authors: R
authors: Lange
authors: Robert
authors: R
authors: Bauernschmitt
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000235:genetics*; D018836:Inflammation Mediators / Q000097:blood; D008875:Middle Aged; D019990:Perioperative Care / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D011446:Prospective Studies; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*
chemical_list: D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha