Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) single nucleotide polymorphisms: Importance in ARDS in septic pediatric critically ill patients

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• 作者：Z.M. Azevedo^a ; ¹ ; ^{zina@iff.fiocruz.br} ; D.B. Moore^b ; ¹ ; ^{danimoore@iff.fiocruz.br} ; F.C. Lima^a ; ^{felimasetta@gmail.com} ; C.C. Cardoso^c ; ^{cynthia@ioc.fiocruz.br} ; R. Bougleux^d ; ^{renata.bougleux@gmail.com} ; G.I. Matos^d ; ^{guilhermeimatos@gmail.com} ; R.A. Luz^d ; ^{ricardoalvesluz@yahoo.com.br} ; P. Xavier-Elsas^e ; ^{pxelsas@yahoo.com.br} ; E.P. Sampaio^c ; ^{esampaio@ioc.fiocruz.br} ; M.I. Gaspar-Elsas^d ; ² ; ^{elsas@iff.fiocruz.br} ; M.O. Moraes^c ; ² ; ^{mmoraes@fiocruz.br}
• 关键词：Sepsis ; Children ; Tumor necrosis factor ; Lymphotoxin alpha ; Acute respiratory distress syndrome ; Genetic polymorphism
• 出版年：2012
• 期刊代码：75_01988859
• 类别：bio
• 出版时间：June, 2012
• 卷：73
• 期：6
• 页码：661-667
• 文件大小：260 K

摘要

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/鈭?63A/鈭?08G; 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 鈭?08A 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 鈭?63A carrier status (OR = 1.82; p = 0.01). After stratification according to age, this outcome remained significantly associated with the 鈭?08GA 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 (): NCT00792883.