Genetic polymorphisms of apolipoprotein E4 and tumor necrosis factor beta as predisposing factors for increased inflammatory cytokines after cardiopulmonary bypass.

OBJECTIVE: Cardiopulmonary bypass induces a rise in cytokines released by activated monocytes. The apolipoprotein E and the tumor necrosis factor beta polymorphisms are risk factors for atherosclerosis. The aim of the study was to investigate whether the genetic variants of apolipoprotein E (APOE*E4) and tumor necrosis factor beta (TNFB*A329G) affect cytokine release after cardiopulmonary bypass.

METHODS: Thirty-eight patients underwent standard coronary artery bypass grafting procedures. Genotyping for APOE*E4 and TNFB*A329G was performed. Concentrations of interleukin 8 and tumor necrosis factor alpha were measured for 48 hours after surgery. Clinical data were collected prospectively.

RESULTS: Fourteen patients (37%) carried the combination non-APOE*E4/wild-type TNFB*A329, 12 patients (32%) showed non-APOE*E4/TNFB*A329G, 9 patients (24%) had APOE*E4/TNFB*A329G, and 3 patients (7%) had APOE*E4/wild-type TNFB*A329. Total amount of tumor necrosis factor alpha was significantly higher in patients carrying the combination APOE*E4/TNFB*A329 than in those carrying non-APOE*E4/wild-type TNFB*A329 (P <.0001). Clinical data were similar except for intubation time and amount of transfusion, which were significantly increased in patients with genetic polymorphisms (P =.022, P =.033).

CONCLUSION: Presence of TNFB*A329G polymorphism in addition to APOE*E4 variant is associated with significantly higher releases of interleukin 8 and tumor necrosis factor alpha, prolonged intubation, and increased transfusion relative to patients without genetic variants. Preoperative determination of APOE/TNFB genotypes in patients undergoing coronary artery bypass grafting may lead to additional perioperative measures to ameliorate systemic inflammatory response.