Angiotensin-converting enzyme insertion/deletion polymorphism is not associated with susceptibility and outcome in sepsis and acute respiratory distress syndrome

Objective: The insertion/deletion (I/D) of a 289 base pair Alu repeat sequence polymorphism in the angiotensin-converting enzyme gene (ACE) has been shown to predict susceptibility and outcome in the acute respiratory distress syndrome (ARDS). We hypothesized that the I/D polymorphism also confers susceptibility to sepsis and is a predisposing factor for morbidity and mortality of patients with severe sepsis. Design and setting: Case-control study including 212 consecutive patients fulfilling criteria for severe sepsis admitted to a Spanish network of postsurgical and critical care units, and 364 population-based controls. Susceptibility to severe sepsis was evaluated as primary outcome; mortality in severe sepsis, susceptibility to sepsis-induced ARDS, and mortality in sepsis-induced ARDS were examined as secondary outcomes. An additive model of inheritance in which patients were classified into three genotype groups (II, ID, and DD) was used for association testing. Measurements and results: Genotype and allele frequencies of I/D were distributed similarly in all septic, ARDS, and non-ARDS patients and in population-based controls. ACE I/D polymorphism was not associated with severe sepsis susceptibility or mortality. The ACE I/D polymorphism was associated neither with sepsis-induced ARDS susceptibility (p=0.895) or mortality (p=0.950). These results remained nonsignificant when adjusted for other covariates using multiple logistic regression analysis or Kaplan-Meier estimates of 28-day survival. Conclusions: Our data do not support an association of the ACE gene I/D polymorphism with susceptibility or mortality in severe sepsis or with sepsis-induced ARDS in Spanish patients.