（）启动子多态性（rs3063368，rs755622）预测心脏手术后的急性肾损伤和死亡。
The () Promoter Polymorphisms (rs3063368, rs755622) Predict Acute Kidney Injury and Death after Cardiac Surgery.
作者信息
Averdunk Luisa, Bernhagen Jürgen, Fehnle Karl, Surowy Harald, Lüdecke Hermann-Josef, Mucha Sören, Meybohm Patrick, Wieczorek Dagmar, Leng Lin, Marx Gernot, Leaf David E, Zarbock Alexander, Zacharowski Kai, Bucala Richard, Stoppe Christian
机构信息
Department of Intensive Care Medicine, University Hospital Aachen, Rheinisch Westphälische Technische Hochschule Aachen, 52074 Aachen, Germany.
Institute of Human Genetics and Department of Pediatrics, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany.
出版信息
J Clin Med. 2020 Sep 11;9(9):2936. doi: 10.3390/jcm9092936.
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 (rs5844572/rs3063368,"-794") and G>C single-nucleotide polymorphism (rs755622,-173) in the gene promoter are related to postoperative outcome.
METHODS
In 1116 patients undergoing cardiac surgery, the gene polymorphisms were analyzed and serum MIF was measured by ELISA in 100 patients.
RESULTS
Patients with at least one extended repeat allele (CATT) had a significantly higher risk of acute kidney injury (AKI) compared to others (23% vs. 13%; OR 2.01 (1.40-2.88), = 0.0001). Carriers of CATT were also at higher risk of death (1.8% vs. 0.4%; OR 5.12 (0.99-33.14), = 0.026). The GC genotype was associated with AKI (20% vs. GG/CC:13%, OR 1.71 (1.20-2.43), = 0.003). Multivariate analyses identified CATT predictive for AKI (OR 2.13 (1.46-3.09), < 0.001) and death (OR 5.58 (1.29-24.04), = 0.021). CATT was associated with higher serum MIF before surgery (79.2 vs. 50.4 ng/mL, = 0.008).
CONCLUSION
The CATT allele associates with a higher risk of AKI and death after cardiac surgery, which might be related to chronically elevated serum MIF. Polymorphisms in the gene may constitute a predisposition for postoperative complications and the assessment may improve risk stratification and therapeutic guidance.
背景
心脏手术后巨噬细胞移动抑制因子（MIF）水平显著升高，并影响术后炎症反应。本研究旨在分析基因启动子中的CATT多态性（rs5844572/rs3063368，“-794”）和G>C单核苷酸多态性（rs755622，-173）是否与术后结局相关。
方法
对1116例行心脏手术的患者进行基因多态性分析，并采用酶联免疫吸附测定法（ELISA）对100例患者测定血清MIF。
结果
与其他患者相比，至少有一个延长重复等位基因（CATT）的患者发生急性肾损伤（AKI）的风险显著更高（23%对13%；比值比[OR]2.01[1.40-2.88]，P=0.0001）。CATT携带者死亡风险也更高（1.8%对0.4%；OR 5.12[0.99-33.14]，P=0.026）。GC基因型与AKI相关（20%对GG/CC：13%，OR 1.71[1.20-2.43]，P=0.003）。多因素分析确定CATT可预测AKI（OR 2.13[1.46-3.09]，P<0.001）和死亡（OR 5.58[1.29-24.04]，P=0.021）。CATT与术前较高的血清MIF相关（79.2对50.4 ng/mL，P=0.008）。
结论
CATT等位基因与心脏手术后发生AKI和死亡的较高风险相关，这可能与血清MIF长期升高有关。该基因的多态性可能构成术后并发症的易患因素，这种评估可能改善风险分层和治疗指导。
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