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A single nucleotide polymorphism of macrophage migration inhibitory factor is related to inflammatory response in coronary bypass surgery using cardiopulmonary bypass.
Authors:Lutz E Lehmann  Stefan Schroeder  Wolfgang Hartmann  Oliver Dewald  Malte Book  Stefan U Weber  Jens-Christian Schewe  Frank Stüber
Institution:Klinik und Poliklinik für An?sthesie und operative Intensivmedizin der Universit?t Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany. Lutz.Lehmann@ukb-bonn.de
Abstract: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 12h postoperatively. In off-pump patients, blood samples were collected before stabilizer placement, after removal of the stabilizer and 12h 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 12h 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.
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