Tumor necrosis factor-α -863 C/A promoter polymorphism affects the inflammatory response after cardiac surgery

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.