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).


CONCLUSIONS
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.
Grünenfelder
Jürg
J
Clinic for Cardiovascular Surgery, University Hospital Zürich, Zurich, Switzerland. jurg.grunenfelder@chi.usz.ch
Umbehr
Martin
M
Plass
Andre
A
Bestmann
Lukas
L
Maly
Friedrich E
FE
Zünd
Gregor
G
Turina
Marko
M
D000368:Aged; D000483:Alleles; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism*; D002315:Cardiopulmonary Bypass; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics / Q000601:surgery; D003326:Coronary Circulation / Q000502:physiology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D016207:Cytokines; D005819:Genetic Markers; D018836:Inflammation Mediators; D016209:Interleukin-8; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha