Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS One. 2011 May 9;6(5):e19469. doi: 10.1371/journal.pone.0019469.
Nuclear factor-κB (NF-κB) is required for transcription of many pro-inflammatory genes and has been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). We hypothesized that a known functional polymorphism in the promoter of the NFKB1 gene may affect susceptibility to and outcome from ARDS.
A case control study was conducted among a cohort of patients admitted to the intensive care unit (ICU) with risk factors for the development of ARDS. 379 patients with ARDS and 793 at-risk controls were studied. Patients were followed for 60 days with development of ARDS as a primary outcome; ARDS-related mortality and organ dysfunction were secondary outcomes.
Patients homozygous for the 4 base pair deletion in the promoter of NFKB1 (del/del) did not have an increased odds ratio (OR) of developing ARDS in unadjusted analysis but were more likely to develop ARDS in the presence of a significant interaction between the del/del genotype and age (OR 5.21, 95% CI 1.35-20.0). In multivariate analysis, patients with ARDS and the del/del genotype also had increased 60 day mortality (HR 1.54, 95% CI 1.01-2.36) and more severe daily organ dysfunction (P<.001) when compared to ARDS patients with other genotypes.
The del/del genotype is associated with an age-dependent increase in odds of developing ARDS. Patients with the del/del genotype and ARDS also have increased hazard of 60 day mortality and more organ failure.
核因子-κB(NF-κB)是许多促炎基因转录所必需的,并且与急性呼吸窘迫综合征(ARDS)的发病机制有关。我们假设 NFKB1 基因启动子中的一个已知功能多态性可能会影响 ARDS 的易感性和结局。
在 ICU 中具有发生 ARDS 危险因素的患者队列中进行了病例对照研究。共研究了 379 例 ARDS 患者和 793 例高危对照。对患者进行了 60 天的随访,以 ARDS 的发生为主要结局;ARDS 相关死亡率和器官功能障碍为次要结局。
在未调整分析中,NFKB1 启动子中存在 4 个碱基缺失的纯合子(del/del)患者发生 ARDS 的优势比(OR)没有增加,但在 del/del 基因型与年龄之间存在显著交互作用的情况下,发生 ARDS 的可能性更大(OR 5.21,95%CI 1.35-20.0)。在多变量分析中,与具有其他基因型的 ARDS 患者相比,患有 ARDS 且具有 del/del 基因型的患者在 60 天时的死亡率(HR 1.54,95%CI 1.01-2.36)和每日器官功能障碍更严重(P<.001)。
del/del 基因型与年龄相关的 ARDS 发生几率增加有关。患有 del/del 基因型和 ARDS 的患者 60 天死亡率和器官衰竭的风险也增加。