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Eur J Cardiothorac Surg 2006;30:59-63
© 2006 Elsevier Science NL

A single nucleotide polymorphism of macrophage migration inhibitory factor is related to inflammatory response in coronary bypass surgery using cardiopulmonary bypass

^a Klinik und Poliklinik für Anästhesie und operative Intensivmedizin der Universität Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany
^b Klinik für Anästhesie und operative Intensivmedizin, Westküstenklinikum, Esmarchstr. 50, 25746 Heide, Germany
^c Institut für Neuropathologie der Universität Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany
^d Klinik und Poliklinik für Herzchirurgie der Universität Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany

Received 18 December 2005; received in revised form 30 January 2006; accepted 31 January 2006.

^_* Corresponding author. Tel.: +49 228 287 6018; fax: +49 228 287 6754. (Email: Lutz.Lehmann{at}ukb.uni-bonn.de).

Objective: Cardiac surgery causes induction and release of inflammatory mediators that may be regulated by genetic background. Macrophage migration inhibitory factor (MIF) is a proinflammatory mediator that is known to be up-regulated in patients undergoing cardiac operations. Here we analyzed genotype distribution and allele frequency of the MIF-173*G/C single nucleotide polymorphism (SNP) and MIF plasma levels in patients undergoing surgical revascularization with (on-pump, n = 45) and without (off-pump, n = 34) cardiopulmonary bypass (CPB). Methods: Genotyping was performed using a real-time PCR-based system with a hybridization probe system specific for the MIF-173*G/C SNP. In on-pump patients, blood samples were drawn before start of CPB, after termination of CPB and 12 h postoperatively. In off-pump patients, blood samples were collected before stabilizer placement, after removal of the stabilizer and 12 h postoperatively. MIF levels were measured using ELISA technique. Results: Genotype distribution and allele frequencies were comparable between on-pump and off-pump patients. When comparing patients according to MIF genotype, a significant increase of MIF plasma levels after completed coronary bypass grafting using CPB was found in patients heterozygous for the MIF-173*G/C SNP (p < 0.05). Moreover, on-pump patients showed significantly decreased MIF plasma levels after 12 h postoperatively (p < 0.05). In off-pump patients, MIF plasma levels were not significantly different over the time-course and were independent of the genotype. Conclusions: Patients carrying the C-allele showed significantly increased levels of the proinflammatory cytokine MIF compared to G/G homozygous when revascularization was carried out using CPB. The G/C genotype may be associated with a severe inflammatory reaction and therefore preoperative screening could be beneficial for patients undergoing cardiac surgery using CPB.

Key Words: MIF • Promoter • Polymorphism • Coronary artery bypass graft • Cardiopulmonary bypass