Common variants of NFE2L2 gene predisposes to acute respiratory distress syndrome in patients with severe sepsis.
Common variants of NFE2L2 gene predisposes to acute respiratory distress syndrome in patients with severe sepsis.
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DOI：
10.1186/s13054-015-0981-y
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发表时间：
2015-06-16
期刊：
影响因子：
--
通讯作者：
GRECIA and GEN-SEP networks
中科院分区：
文献类型：
--
作者：
Acosta-Herrera M;Pino-Yanes M;Blanco J;Ballesteros JC;Ambrós A;Corrales A;Gandía F;Subirá C;Domínguez D;Baluja A;Añón JM;Adalia R;Pérez-Méndez L;Flores C;Villar J;GRECIA and GEN-SEP networks
本研究的目的是探讨核因子红细胞2样2 （NFE2L2）基因的常见变异是否有助于严重脓毒症患者急性呼吸窘迫综合征（ARDS）的发展。NFE2L2参与对氧化应激的反应，并已被证明与创伤患者ARDS的发展有关。我们进行了一项病例对照研究，纳入了321例西班牙术后和重症监护病房网络中符合严重脓毒症和ARDS国际标准的患者，以及871例基于人群的对照组。对NFE2L2的6个标记单核苷酸多态性（snp）进行基因分型，并对另外34个snp进行代入后，采用logistic回归分析进行与ARDS易感性的相关性检验。经过多次测试调整，我们的分析发现10个紧密连锁不平衡（0.75≤r2≤1）的非编码snp作为单一关联信号与ARDS易感性相关。其中一个snp （rs672961）先前与创伤性ARDS相关，并改变了NFE2L2基因的启动子活性，每T等位基因的优势比为1.93（95%置信区间，1.17-3.18;p = 0.0089）。我们的研究结果支持NFE2L2基因变异参与ARDS易感性，并进一步探索氧化应激反应作为危重患者ARDS危险因素的作用。
The purpose of this study was to investigate whether common variants across the nuclear factor erythroid 2-like 2 (NFE2L2) gene contribute to the development of the acute respiratory distress syndrome (ARDS) in patients with severe sepsis. NFE2L2 is involved in the response to oxidative stress, and it has been shown to be associated with the development of ARDS in trauma patients. We performed a case–control study of 321 patients fulfilling international criteria for severe sepsis and ARDS who were admitted to a Spanish network of post-surgical and critical care units, as well as 871 population-based controls. Six tagging single-nucleotide polymorphisms (SNPs) of NFE2L2 were genotyped, and, after further imputation of additional 34 SNPs, association testing with ARDS susceptibility was conducted using logistic regression analysis. After multiple testing adjustments, our analysis revealed 10 non-coding SNPs in tight linkage disequilibrium (0.75 ≤ r2 ≤ 1) that were associated with ARDS susceptibility as a single association signal. One of those SNPs (rs672961) was previously associated with trauma-induced ARDS and modified the promoter activity of the NFE2L2 gene, showing an odds ratio of 1.93 per T allele (95 % confidence interval, 1.17–3.18; p = 0.0089). Our findings support the involvement of NFE2L2 gene variants in ARDS susceptibility and reinforce further exploration of the role of oxidant stress response as a risk factor for ARDS in critically ill patients.
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