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NFKB1 启动子插入/缺失多态性影响白种人急性呼吸窘迫综合征的风险和预后。

An NFKB1 promoter insertion/deletion polymorphism influences risk and outcome in acute respiratory distress syndrome among Caucasians.

机构信息

Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.

出版信息

PLoS One. 2011 May 9;6(5):e19469. doi: 10.1371/journal.pone.0019469.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

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。

方法

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。

结果

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)。

结论

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6f8/3090449/3ac0b4c5b436/pone.0019469.g001.jpg

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