Association of TNF2, a TNF-α promoter polymorphism, with septic shock susceptibility and mortality -: A multicenter study
Association of TNF2, a TNF-α promoter polymorphism, with septic shock susceptibility and mortality -: A multicenter study
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DOI：
10.1001/jama.282.6.561
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发表时间：
1999-08-11
影响因子：
120.7
通讯作者：
Dhainaut, JF
中科院分区：
文献类型：
--
作者：
Mira, JP;Cariou, A;Dhainaut, JF
肿瘤坏死因子α（TNF-α）被认为是感染性休克发病机制的核心细胞因子。TNF-α基因多态性与TNF-α的产生和某些严重感染的负性结局有关。目的研究TNF-α 2等位基因在感染性休克患者中的频率，并确定该等位基因是否与感染性休克的发生和结局有关。研究对象：89名感染性休克患者和87名健康的无血缘关系的献血者。主要结果：感染性休克患者和死亡患者中TNF-2等位基因的频率以及相应的TNF-α浓度水平。结果感染性休克患者的死亡率为54%，与简化急性生理评分（SAPS II）值预测的死亡率一致。对照组和感染性休克患者的多态性频率仅在TNF 2等位基因上存在差异（感染性休克组和对照组分别为39%和18%，P = 0.002）。在感染性休克患者中，TNF 2多态性频率在死亡组中显著更高（52% vs 24%）。P =.008）。TNF 2和TNF 1多态性分别有68%和52%的患者TNF-α浓度较高，但其中位数（48 pg/mL vs 29 pg/mL）无统计学差异（P =.31）。在控制了年龄和SAPS II评分的死亡概率后，多因素Logistic回归分析显示，在SAPS II评分相同的等级下，携带TNF 2等位基因的患者死亡风险是携带TNF 2等位基因患者的3.7倍（95%可信区间为1.37-20.24）。
Context Tumor necrosis factor alpha (TNF-alpha) is believed to be a cytokine central to pathogenesis of septic shock. TNF2, a polymorphism within the TNF-alpha gene pro meter, has been associated with enhanced TNF-alpha production and negative outcome in some severe infections.Objectives To investigate the frequency of the TNF2 allele in patients with septic shock and to determine whether the allele is associated with the occurrence and outcome of septic shock.Design Multicenter case-control study conducted from March 1996 to June 1997,Setting Seven medical intensive care units in university hospitals.Subjects Eighty-nine patients with septic shock and 87 healthy unrelated blood donors.Main Outcome Measures Frequency of the TNF2 allele among patients with septic shock and among those who died and the level of corresponding TNF-alpha concentrations.Results Mortality among patients with septic shock was 54%, consistent with the predicted mortality from the Simplified Acute Physiologic Score (SAPS II) value. The polymorphism frequencies of the controls and the patients with septic shock differed only at the TNF2 allele (39% vs 18% in the septic shock and control groups, respectively, P =.002). Among the septic shock patients, TNF2 polymorphism frequency was significantly greater among those who had died (52% vs 24% in the survival group. P =.008). Concentrations of TNF-alpha were higher in 68% and 52% with the TNF2 and TNF1 polymorphisms, respectively, but their median Values (48 pg/mL vs 29 pg/mL) were not statistically different (P =.31). After controlling for age and the probability of death, derived by the SAPS II score, multiple logistic regression analysis showed that, for the same rank of SAPS ii value, patients with the TNF2 allele had a 3.7-fold risk of death (95% confidence interval, 1.37-20.24).Conclusion The TNF2 allele is strongly associated with susceptibility to septic shock and death due to septic shock.