Tumor necrosis factor gene polymorphism is associated with enhanced systemic inflammatory response and increased cardiopulmonary morbidity after cardiac surgery
Tumor necrosis factor gene polymorphism is associated with enhanced systemic inflammatory response and increased cardiopulmonary morbidity after cardiac surgery
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DOI：
10.1213/01.ane.0000078574.76915.11
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发表时间：
2003-10-01
影响因子：
5.7
通讯作者：
Ricksten, SE
中科院分区：
文献类型：
--
作者：
Tomasdottir, H;Hjartarson, H;Ricksten, SE
心脏搭桥术诱导以心肺功能改变为特征的全身炎症反应。这种发病率的介质是细胞因子肿瘤坏死因子（TNF）-α和白细胞介素。TNF基因座内的基因多态性与严重创伤和脓毒症中TNF-α水平升高和高死亡率相关。我们评估了择期心脏手术患者TNF位点双等位基因多态性与促炎细胞因子释放和心肺疾病发病率的关系。在95例连续接受常规心脏手术的患者中研究了TNF基因型、TNF-α血浆浓度、白细胞介素-6和心肺疾病发病率。TNF基因型通过固相微测序法测定。TNFB 2等位基因纯合子患者（n = 42）的TNF-α峰值浓度较大（11.3 ± 1.3 vs 7.8 ± 0.7 pg/mL; P = 0.013）和白细胞介素-6（153 +/-27 vs 87 +/-7 pg/mL; P = 0.010），与TNFB 1纯合子或杂合子患者（n = 53）相比。TNFB 2纯合子左室功能不全的发生率较高，（31% vs 9%; P = 0.029;比值比3.84 [95%置信区间，1.40 - 24.31]），术后肺功能不全（24%对6%; P = 0.016;比值比5.21 [95%置信区间，1.49 - 18.3]）和较低的肺氧合指数（29 +/-1.9对36.1 +/-1.8; P = 0.013）。TNFB 2等位基因纯合子患者在心脏手术后可能会发生增强的全身炎症反应，并增加心肺疾病的风险。
Cardiopulmonary bypass induces a systemic inflammatory response characterized by alterations in cardiopulmonary function. Mediators for this morbidity are the cytokines tumor necrosis factor (TNF)-alpha and interleukins. A genomic polymorphism within the TNF locus is associated with increased TNF-alpha levels and high mortality in severe trauma and sepsis. We assessed the relationship of biallelic polymorphisms of the TNF locus in patients undergoing elective cardiac surgery to release of proinflammatory cytokines and cardiopulmonary morbidity. TNF genotypes, plasma concentrations of TNF-a, interleukin-6, and cardiopulmonary morbidity were studied in 95 unselected, consecutive patients undergoing routine cardiac surgery. TNF genotypes were determined by the solid-phase minisequencing method. Patients homozygous for the TNFB2 allele (n = 42) displayed larger peak concentrations of TNF-alpha (11.3 +/- 1.3 versus 7.8 +/- 0.7 pg/mL; P = 0.013) and interleukin-6 (153 +/- 27 versus 87 +/- 7 pg/mL; P = 0.010) when compared with patients homozygous or heterozygous for TNFB1 (n = 53). The TNFB2 homozygotes had a higher incidence of left ventricular dysfunction (31% versus 9%; P = 0.029; odds ratio 3.84 [95% confidence interval, 1.40-24.31), postoperative pulmonary dysfunction (24% versus 6%; P = 0.016; odds ratio 5.21 [95% confidence interval, 1.49-18.3]), and a lower pulmonary oxygenation index (29 +/- 1.9 versus 36.1 +/- 1.8; P = 0.013). Patients homozygous for the TNFB2 allele may develop an enhanced systemic inflammatory response with an increased risk of cardiopulmonary morbidity after cardiac surgery.