Interleukin-1 Receptor–Associated Kinase 3 Gene Associates with Susceptibility to Acute Lung Injury

• DOI: 10.1165/rcmb.2010-0292oc
• Publication Date: 2011-02-05T05:20:40Z
• Authors: María Pino-Yanes; Shwu-Fan Ma; Xiaoguang Sun; Paula Tejera; Almudena Corrales; Jesús Blanco; Lina Pérez-Méndez; Elena Espinosa; Arturo Muriel; Lluis Blanch; Joe G. N. Garcia; Jesús Villar; Carlos Flores
• Keywords: Adult; Male; 0303 health sciences; Binding Sites; Acute Lung Injury; Endothelial Cells; Middle Aged; 3. Good health; Intensive Care Units; 03 medical and health sciences; Interleukin-1 Receptor-Associated Kinases; Logistic Models; Phenotype; Gene Frequency; Genes, Reporter; Case-Control Studies; Linear Models; Odds Ratio; Humans; Female; Genetic Predisposition to Disease; Cells, Cultured; Aged

Sepsis is the most common cause of acute lung injury (ALI), leading to organ dysfunction and death in critically ill patients. Previous studies associated variants interleukin-1 receptor-associated kinase genes (IRAKs) with differential immune responses pathogens outcomes during sepsis, revealed that increased expression levels IRAK3 gene were correlated poor sepsis. Here we explored whether susceptibility to, of, severe After our discovery polymorphism, genotyped a subset seven single-nucleotide polymorphisms (SNPs) 336 population-based control subjects 214 patients collected as part prospective study adults from Spanish network intensive care units. Whereas SNPs not rs10506481 showed significant association development ALI among sepsis (P = 0.007). The remained after adjusting for multiple comparisons, population stratification, clinical variables (odds ratio, 2.50; 95% confidence interval, 1.15-5.47; P 0.021). By imputation, three additional independently < 0.01). One these (rs1732887) predicted disruption putative human-mouse conserved transcription factor binding site, demonstrated functional effects vitro 0.017). Despite need replication independent studies, data suggest may be determinants sepsis-induced ALI.