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J Thorac Cardiovasc Surg 2004;128:92-97
© 2004 The American Association for Thoracic Surgery

Cardiopulmonary support and physiology

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

^a Clinic for Cardiovascular Surgery, University Hospital Zürich, Zürich, Switzerland
^b Institute of Clinical Chemistry, University Hospital Zürich, Zürich, Switzerland

Received for publication October 15, 2003; revisions received February 12, 2004; accepted for publication February 27, 2004.

^* Address for reprints: Jürg Grünenfelder, MD, Clinic for Cardiovascular Surgery, University Hospital Zürich, Rämistrasse 100, 8091 Zürich, Switzerland
jurg.grunenfelder{at}chi.usz.ch

OBJECTIVE: Cardiopulmonary bypass induces a rise in cytokines released by activated monocytes. The apolipoprotein E and the tumor necrosis factor ß 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 ß (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 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 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 , 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.

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