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Averdunk, Luisa; Bernhagen, Jürgen; Fehnle, Karl; Surowy, Harald; Luedecke, Hermann-Josef; Mucha, Soeren; Meybohm, Patrick; Wieczorek, Dagmar; Leng, Lin; Marx, Gernot; Leaf, David E.; Zarbock, Alexander; Zacharowski, Kai; Bucala, Richard und Stoppe, Christian (2020): TheMacrophage Migration Inhibitory Factor(MIF) Promoter Polymorphisms (rs3063368, rs755622) Predict Acute Kidney Injury and Death after Cardiac Surgery. In: Journal of Clinical Medicine, Bd. 9, Nr. 9, 2936

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Abstract

Background: Macrophage Migration Inhibitory Factor (MIF) is highly elevated after cardiac surgery and impacts the postoperative inflammation. The aim of this study was to analyze whether the polymorphisms CATT(5-7)(rs5844572/rs3063368,"-794") and G>C single-nucleotide polymorphism (rs755622,-173) in theMIFgene promoter are related to postoperative outcome. Methods: In 1116 patients undergoing cardiac surgery, theMIFgene polymorphisms were analyzed and serum MIF was measured by ELISA in 100 patients. Results: Patients with at least one extended repeat allele (CATT(7)) had a significantly higher risk of acute kidney injury (AKI) compared to others (23% vs. 13%;OR 2.01 (1.40-2.88),p= 0.0001). Carriers of CATT(7)were also at higher risk of death (1.8% vs. 0.4%;OR 5.12 (0.99-33.14),p= 0.026). The GC genotype was associated with AKI (20% vs. GG/CC:13%, OR 1.71 (1.20-2.43),p= 0.003). Multivariate analyses identified CATT(7)predictive for AKI (OR 2.13 (1.46-3.09),p< 0.001) and death (OR 5.58 (1.29-24.04),p= 0.021). CATT(7)was associated with higher serum MIF before surgery (79.2 vs. 50.4 ng/mL,p= 0.008). Conclusion: The CATT(7)allele associates with a higher risk of AKI and death after cardiac surgery, which might be related to chronically elevated serum MIF. Polymorphisms in theMIFgene may constitute a predisposition for postoperative complications and the assessment may improve risk stratification and therapeutic guidance.

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