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载脂蛋白E4和肿瘤坏死因子β的基因多态性作为体外循环后炎症细胞因子增加的易感因素。

Genetic polymorphisms of apolipoprotein E4 and tumor necrosis factor beta as predisposing factors for increased inflammatory cytokines after cardiopulmonary bypass.

作者信息

Grünenfelder Jürg, Umbehr Martin, Plass Andre, Bestmann Lukas, Maly Friedrich E, Zünd Gregor, Turina Marko

机构信息

Clinic for Cardiovascular Surgery, University Hospital Zürich, Zurich, Switzerland.

出版信息

J Thorac Cardiovasc Surg. 2004 Jul;128(1):92-7. doi: 10.1016/j.jtcvs.2004.02.022.

Abstract

OBJECTIVE

Cardiopulmonary bypass induces a rise in cytokines released by activated monocytes. The apolipoprotein E and the tumor necrosis factor beta polymorphisms are risk factors for atherosclerosis. The aim of the study was to investigate whether the genetic variants of apolipoprotein E (APOEE4) and tumor necrosis factor beta (TNFBA329G) affect cytokine release after cardiopulmonary bypass.

METHODS

Thirty-eight patients underwent standard coronary artery bypass grafting procedures. Genotyping for APOEE4 and TNFBA329G was performed. Concentrations of interleukin 8 and tumor necrosis factor alpha were measured for 48 hours after surgery. Clinical data were collected prospectively.

RESULTS

Fourteen patients (37%) carried the combination non-APOEE4/wild-type TNFBA329, 12 patients (32%) showed non-APOEE4/TNFBA329G, 9 patients (24%) had APOEE4/TNFBA329G, and 3 patients (7%) had APOEE4/wild-type TNFBA329. Total amount of tumor necrosis factor alpha was significantly higher in patients carrying the combination APOEE4/TNFBA329 than in those carrying non-APOEE4/wild-type TNFBA329 (P <.0001). Clinical data were similar except for intubation time and amount of transfusion, which were significantly increased in patients with genetic polymorphisms (P =.022, P =.033).

CONCLUSION

Presence of TNFBA329G polymorphism in addition to APOEE4 variant is associated with significantly higher releases of interleukin 8 and tumor necrosis factor alpha, prolonged intubation, and increased transfusion relative to patients without genetic variants. Preoperative determination of APOE/TNFB genotypes in patients undergoing coronary artery bypass grafting may lead to additional perioperative measures to ameliorate systemic inflammatory response.

摘要

目的

体外循环会导致活化单核细胞释放的细胞因子增加。载脂蛋白E和肿瘤坏死因子β基因多态性是动脉粥样硬化的危险因素。本研究的目的是调查载脂蛋白E(APOEE4)和肿瘤坏死因子β(TNFBA329G)的基因变异是否会影响体外循环后的细胞因子释放。

方法

38例患者接受了标准冠状动脉搭桥手术。对APOEE4和TNFBA329G进行基因分型。术后48小时测量白细胞介素8和肿瘤坏死因子α的浓度。前瞻性收集临床数据。

结果

14例患者(37%)携带非APOEE4/野生型TNFBA329组合,12例患者(32%)为非APOEE4/TNFBA329G,9例患者(24%)为APOEE4/TNFBA329G,3例患者(7%)为APOEE4/野生型TNFBA329。携带APOEE4/TNFBA329组合的患者肿瘤坏死因子α的总量显著高于携带非APOEE4/野生型TNFBA329的患者(P<.0001)。除插管时间和输血量外,临床数据相似,基因多态性患者的插管时间和输血量显著增加(P=.022,P=.033)。

结论

与无基因变异的患者相比,除APOEE4变异外,存在TNFBA329G多态性与白细胞介素8和肿瘤坏死因子α的释放显著增加、插管时间延长和输血增加有关。对接受冠状动脉搭桥手术的患者进行术前APOE/TNFB基因型测定可能会导致采取额外的围手术期措施来改善全身炎症反应。

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