Increased mortality in septic shock with the 4G/4G genotype of plasminogen activator inhibitor 1 in patients of white descent
Increased mortality in septic shock with the 4G/4G genotype of plasminogen activator inhibitor 1 in patients of white descent
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DOI：
10.1007/s00134-007-0695-y
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发表时间：
2007-08-01
影响因子：
38.9
通讯作者：
Nicolas, Josep-Maria
中科院分区：
文献类型：
--
作者：
Garcia-Segarra, Gloria;Espinosa, Gerard;Nicolas, Josep-Maria
目的：评价PAI-1基因4G/5G多态性对脓毒症危重患者器官衰竭发生和预后的影响。设计和设置：前瞻性，观察性研究，在一所大学医院的重症监护病房。患者：224例连续住院患者。干预措施：记录流行病学数据、严重程度评分和原发感染部位。对PAI-1、TNF-β和IL 1-ra基因进行DNA基因分型，并测量血浆PAI-1抗原和D-二聚体。测量：主要结局变量为器官功能障碍和死亡率。结果：88名受试者在进入ICU时或入院后48小时内出现感染性休克。4G等位基因的纯合子表现出比4G/5G和5G/5G受试者更高的PAI-1抗原和D-二聚体血浆浓度。ICU死亡率4G/4G为44.0%，4G/5G为23.4%，5G/5G为12.5%，主要原因为多器官功能衰竭。在入院时调整SAPS II后，与脓毒性休克ICU死亡率独立相关的基因型为TNF-B2/B2（OR 2.83，1.04 - 7.67）和PAI-1 4G/4G（OR 2.23，1.02 - 4.85）。PAI-1基因型不能决定感染的易感性或非脓毒性全身炎症反应综合征、脓毒症、严重脓毒症和院内感染性休克的预后。结论：PAI-1基因的4G纯合性增加了感染性休克成人患者由于更大的器官衰竭而死亡的风险。
Objective: To evaluate the effect of the 4G/5G PAI-1 gene polymorphism on the development of organ failure and outcome in critically ill patients with septic syndromes. Design and setting: Prospective, observational study in a medical intensive care unit of a university hospital. Patients: 224 consecutively admitted patients. Interventions: Epidemiological data, severity scores, and the primary site of infection were recorded. DNA genotyping of the PAI-1, TNF-beta, and IL1-ra genes, and measurement of plasma PAI-1 antigen and D-dimer were carried out. Measurements: The primary outcome variables were organ dysfunction and mortality. Results: Eighty-eight subjects had septic shock at ICU entry or within 48 h from admission. Homozygotes for the 4G allele exhibited higher plasma concentrations of PAI-1 antigen and D-dimer than 4G/5G and 5G/5G subjects). ICU mortality was 44.0% in patients with 4G/4G, 23.4% in 4G/5G and 12.5% in 5G/5G, mainly due to multiorgan failure. After adjusting for SAPS II at admission the genotypes independently associated with ICU mortality in septic shock were TNF-B2/B2 (OR 2.83, 1.04-7.67) and 4G/4G of PAI-1 (OR 2.23, 1.02-4.85). The PAI-1 genotype did not determine susceptibility to infection or the outcome in nonseptic systemic inflammatory response syndrome, sepsis, severe sepsis, and nosocomial septic shock. Conclusions: Homozygosity for 4G of the PAI-1 gene confers an increase in the risk of mortality in adult patients with septic shock due to a greater organ failure.