Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) single nucleotide polymorphisms: Importance in ARDS in septic pediatric critically ill patients
Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) single nucleotide polymorphisms: Importance in ARDS in septic pediatric critically ill patients
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DOI：
10.1016/j.humimm.2012.03.007
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发表时间：
2012-06-01
期刊：
影响因子：
2.7
通讯作者：
Moraes, M. O.
中科院分区：
文献类型：
--
作者：
Azevedo, Z. M.;Moore, D. B.;Moraes, M. O.
越来越多的证据表明，遗传背景影响脓毒症的结果，尽管医学进步仍然是发病率和死亡率的主要原因。本研究旨在评估SNPs LTA+252 A>G、TNF-863 C>A和TNF-308 G>A对脓毒症、急性呼吸窘迫综合征（ARDS）、脓毒性休克和脓毒症死亡率易感性的影响。在巴西儿科重症监护病房进行了一项前瞻性病例对照研究，包括490名接受机械通气的脓毒症儿科患者和610名健康儿童。没有发现SNP与脓毒症易感性相关。然而，鉴定了对脓毒症具有保护作用的单倍型（+252A/-863A/-308G; OR = 0.65; p = 0.03）。我们进一步观察到TNF-308 GA基因型携带者（OR = 0.29; p = 0.0006）和-308A等位基因携带者（OR = 0.40; p = 0.003）对ARDS的保护作用。此外，TNF-863 CA基因型（OR = 1.83; p = 0.01）和-863 A携带状态（OR = 1.82; p = 0.01）可检测到ARDS风险增加。根据年龄分层后，这一结果仍然与婴儿的-308GA基因型显著相关。最后，发现TNF-308 GA基因型对脓毒症相关死亡率的保护作用（OR = 0.22; p = 0.04）。总体而言，我们的研究结果证明了TNF-308 GA基因型对ARDS和脓毒症死亡结局的保护作用，进一步提供了TNF-863 CA基因型相关的ARDS风险增加的证据。试验注册（www.clinicaltrials.gov）：NCT 00792883。(C)2012年美国组织相容性和免疫遗传学学会。爱思唯尔公司出版All rights reserved.
Accumulating evidence indicates that genetic background influences the outcome of sepsis, which despite medical advances continues to be a major cause of morbidity and mortality. This study aimed to evaluate the influence of SNPs LTA+252A>G, TNF-863C>A and TNF-308G>A on susceptibility to sepsis, acute respiratory distress syndrome (ARDS), septic shock and sepsis mortality. A prospective case-control study was carried out in a Brazilian pediatric intensive care unit and included 490 septic pediatric patients submitted to mechanical ventilation and 610 healthy children. No SNP association was found with respect to sepsis susceptibility. Nevertheless, a haplotype was identified that was protective against sepsis (+252A/-863A/-308G; OR = 0.65; p = 0.03). We further observed protection against ARDS in TNF-308 GA genotype carriers (OR = 0.29; p = 0.0006) and -308A allele carriers (OR = 0.40; p = 0.003). In addition, increased risk for ARDS was detectable with the TNF-863 CA genotype (OR = 1.83; p = 0.01) and the -863A carrier status (OR = 1.82; p = 0.01). After stratification according to age, this outcome remained significantly associated with the -308GA genotype in infants. Finally, protection against sepsis-associated mortality was found for the TNF-308 GA genotype (OR = 0.22; p = 0.04). Overall, our findings document a protective effect of the TNF-308 GA genotype for the ARDS and sepsis mortality outcomes, further providing evidence for an increased risk of ARDS associated with the TNF-863 CA genotype. Trial registration (www.clinicaltrials.gov): NCT00792883. (C) 2012 American Society for Histocompatibility and lmmunogenetics. Published by Elsevier Inc. All rights reserved.