Burzotta Francesco, Iacoviello Licia, Di Castelnuovo Augusto, Zamparelli Roberto, D'Orazio Andria, Amore Concetta, Schiavello Rocco, Donati Maria Benedetta, Maseri Attilio, Possati GianFederico, Andreotti Felicita
Department of Cardiovascular Medicine, Catholic University, Rome, Italy.
J Thromb Thrombolysis. 2003 Dec;16(3):149-54. doi: 10.1023/B:THRO.0000024052.79415.62.
The 4G/5G plasminogen activator inhibitor-1 (PAI-1) promoter polymorphism has been associated with basal PAI-1 levels, with ischemic heart disease, and with adverse prognosis in critically ill patients. We hypothesized it might also influence the acute-phase levels of PAI-1 following coronary bypass surgery.
In 111 consecutive patients undergoing elective coronary bypass surgery, 4G/5G genotyping and serial plasma PAI-1 activity and antigen levels were prospectively measured before surgery, daily up to 72 h, and at discharge. The inflammatory reaction was additionally assessed by white cell count, fibrinogen, interleukin-6, and C-reactive protein levels.
PAI-1 activity and antigen concentrations increased approximately two-fold after surgery, peaking at 48 hours. Carriers of the 4G-allele, compared with 5G/5G homozygotes, showed approximately 20% higher PAI-1 activity and antigen both preoperatively ( P = 0.007 and P = 0.035) and after surgery. White cell count, fibrinogen, interleukin-6, and C-reactive protein values did not differ significantly according to genotypic groups. In multivariate analysis, the 4G/5G genotype was the only significant modulator of postoperative PAI-1 activity (P = 0.003) and the main significant modulator of postoperative PAI-1 antigen (P = 0.013). No significant interaction was found between the effects of time and genotype on postoperative PAI-1. This indicates that the association between 4G/5G and acute-phase PAI-1 levels is secondary to the genotype-related difference of baseline PAI-1.
Postoperative PAI-1 concentrations of patients undergoing elective coronary bypass surgery are higher in carriers of the 4G-allele than in 5G/5G homozygotes as a result of higher baseline values. Knowledge of 4G/5G status may be useful to predict acute-phase PAI-1 concentrations.
4G/5G纤溶酶原激活物抑制剂-1（PAI-1）启动子多态性与基础PAI-1水平、缺血性心脏病以及危重症患者的不良预后相关。我们推测其可能也会影响冠状动脉搭桥手术后PAI-1的急性期水平。
对111例连续接受择期冠状动脉搭桥手术的患者，前瞻性地测定术前、术后每日直至72小时以及出院时的4G/5G基因分型、系列血浆PAI-1活性和抗原水平。另外通过白细胞计数、纤维蛋白原、白细胞介素-6和C反应蛋白水平评估炎症反应。
手术后PAI-1活性和抗原浓度增加约两倍，在48小时达到峰值。与5G/5G纯合子相比，4G等位基因携带者术前（P = 0.007和P = 0.035）和术后PAI-1活性和抗原均高约20%。白细胞计数、纤维蛋白原、白细胞介素-6和C反应蛋白值在各基因型组间无显著差异。多因素分析中，4G/5G基因型是术后PAI-1活性的唯一显著调节因素（P = 0.003）以及术后PAI-1抗原的主要显著调节因素（P = 0.013）。未发现时间和基因型对术后PAI-1的影响之间存在显著交互作用。这表明4G/5G与急性期PAI-1水平之间的关联继发于基线PAI-1的基因型相关差异。
由于基线值较高，择期冠状动脉搭桥手术患者中4G等位基因携带者术后PAI-1浓度高于5G/5G纯合子。了解4G/5G状态可能有助于预测急性期PAI-1浓度。
