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

Autor: Johannes Boehm, Siegmund Braun, Stefan Wagenpfeil, Katharina Hauner, J Grammer, Robert Bauernschmitt, Rüdiger Lange, Wulf Dietrich
Rok vydání: 2010
Předmět:
Zdroj: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. 40(1)
ISSN: 1873-734X
Popis: Objective:Cardiacsurgeryusingcardiopulmonarybypass(CPB)initiatesaninflammatoryresponsethatshowsawideinter-individualrangeand 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-a) release remains unclear. We tested two geneticsingle-nucleotide polymorphisms (SNPs) from the promoterregion of the TNF-agenefor associationswith perioperative TNF-alevel after CPB.Methods:Weprospectivelyincluded122patients,whounderwentelectivecoronaryarterybypassgrafting(CABG).Patientsweregenotyped for TNF-a —863 C/A (rs1800630) and TNF-a —308 G/A (rs1800629). Plasma level of TNF-a was obtained preoperatively, at the end of CPB, 6 h 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-a 863 C/A polymorphism: the major —863 CC variant was associated with higher TNF-a level preoperatively (p = 0.003), after CPB (p = 0.005), and 6 h postoperatively (p = 0.010), independently from CPB time, left ventricle (LV) function and age. Contrarily, the AA allele had lower TNF-a level preoperatively (p = 0.008), after surgery (p = 0.024) and 6 h postoperatively (p = 0.001). For the TNF-a 308 G/A polymorphism, only few significant associations could be observed: —308 GG carriers were associated with lower TNF-a level immediately after CPB (p = 0.020), whereas 308 AA carriers were significantly associated with elevated TNF-a 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-a level. Conclusions: The current study suggests that the major —863 CC variant determines elevated TNF-a level preoperatively and throughout the postoperative course after CPB. # 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
Databáze: OpenAIRE