SHORT COMMUNICATION The effect of NQO1 polymorphism on the inflammatory response in cardiopulmonary bypass C. Selim Isbir 1 * , y , Arzu Ergen 2 , Atike Tekeli 2 , Umit Zeybek 2 , Uzay Gormus 2 and Sinan Arsan 1 1 Department of Cardiovascular Surgery, Marmara University Hospital, Istanbul, Turkey 2 Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University, Capa, Istanbul, Turkey Cardiopulmonary bypass (CPB) has been associated with systemic inflammatory response syndrome (SIRS). Endothelial dysfunction related to non-laminar flow during CPB is known to play a key role in this complex pathology. Antioxidant response element (ARE) dependent NAD(P)H:quinone oxidoreductase 1 (NQO1) promoter is a regulatory element involved in the anti-inflammatory mechanism in vasculature exposed to non-laminar flow. Mutation of the NQO1 could represent a novel anti-inflammatory effect in CPB. The goal of this study was to demonstrate whether genetic variants of NQO1 affect cytokine release after CPB. Eighteen patients who underwent standard coronary artery bypass grafting (CABG) operation were included in the study. Genotyping for NQO1 was performed. Serum Interleukin-6 (IL-6) levels were measured before induction, during CPB after declamping the aorta, and 24 h after operation. Clinical data were collected respectively. Seven patients were NQO1 T carriers and 11 patients were NQO1 T non-carriers. During CPB, IL-6 concentrations were increased in NQO1 T carriers compared to T non-carriers ( p ¼ 0.038). Although ventilation times and blood loss were higher in T carriers these were not statistically significant. Patients with NQO1 T carriers showed significantly higher IL-6 levels during CPB. Non-laminar flow during CPB may diminish the transcriptional activation of the NQO1 in T carriers. Preoperative determination of this novel anti-inflammatory mechanism could be useful to improve operative outcome in CPB. Copyright # 2007 John Wiley & Sons, Ltd. key words — inflammation; cardiopulmonary bypass; NQO1; PCR-RFLP INTRODUCTION Cardiopulmonary bypass (CPB) is known to induce a systemic inflammatory response syndrome (SIRS) that may affect postoperative morbidity and mortality of patients. Several mechanisms including contact activation of blood with non-endothelial surfaces, hypothermia and non-laminar flow are predisposing factors in this complex process. 1–3 Recently functional genomic predisposition became an important bio- logical reason why similar patients can have dramatically different outcomes related to SIRS after surgery. 4–6 Fluid shear stress plays an important role in the maintenance of vascular integrity. Laminar flow and high levels of fluid shear stress are protective against endothelial dysfunction. Exposure of endothelial cells to laminar flow activates NAD(P)H:quinone oxido- reductase 1 (NQO1) promoter which is an important element of the antioxidant response element (ARE), whereas non-laminar flow diminishes antioxidant defense systems. 7,8 Suppression of endogenous anti- cell biochemistry and function Cell Biochem Funct 2008; 26: 534–538. Published online 20 December 2007 in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/cbf.1456 * Correspondence to: Dr C. S. Isbir, MD, Marmara University Hospital, Tophanelioglu cad. No: 13-15, Altunizade, Istanbul, 80200, Turkey. Fax: þ90 212 6351959; Tel: þ90 2124285777, þ90 5324057070. E-mail: isbir@yahoo.com y Associate Professor of Cardiovascular Surgery. Copyright # 2007 John Wiley & Sons, Ltd. Received 24 September 2007 Revised 22 October 2007 Accepted 25 October 2007