Importance of NOD2/CARD15 gene variants for susceptibility to and outcome of sepsis in Turkish children

Objective: Severe sepsis remains a leading cause of morbidity and mortality in children. Given the link to pathogenesis, polymorphisms in genes involved in infection and inflammation may influence the outcomes in patients with sepsis and septic shock. The role of mutations within the innate immunity receptor NOD2/CARD15 has recently been demonstrated as a risk factor for bacteremia and mortality in adult patients with sepsis. The aim of this study was to evaluate the role of mutations of the NOD2/CARD15 gene in pediatric patients with sepsis. Design: Prospective cohort study. Setting: A tertiary care, ten-bed, pediatric intensive care unit. Patients: One hundred twenty-eight patients with sepsis admitted to the pediatric intensive care unit and healthy control group were included. Interventions: Venous blood from the children with sepsis and healthy controls was collected to investigate common polymorphisms (Arg702Trp, Gly908Arg, Leu1007fsincC) within the NOD2/CARD15 gene. Standard polymerase chain reaction restriction fragment length polymorphism technique was used to determine NOD2/CARD15 gene polymorphism. Measurement and Main Results: R702W, G908R, and Leu1007fsinsC variants in the NOD2/CARD15 gene were determined as significant risk factors associated with susceptibility to sepsis (p = .025, p = .031, p = .014, respectively). Sepsis-related mortality was increased in children carrying the Leu1007fsinsC variant (p = .041). Conclusions: The present article is the first report of clinical implications of NOD2/CARD15 gene variants in children with sepsis. Our findings suggest that common polymorphisms in the NOD2/CARD15 gene may play a major role in susceptibility to sepsis and the outcome of sepsis in children. (Pediatr Crit Care Med 2012; 13:e73-e77)