Angiotensin converting enzyme insertion /deletion polymorphism is associated with susceptibility and outcome in acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is an often fatal condition for which a genetic predisposition is postulated, although no specific genes have been identified to date. Angiotensin converting enzyme (ACE) has a potential role in the pathogenesis of ARDS via effects on pulmonary vascular tone/permeability, epithelial cell survival, and fibroblast activation. Forty-seven percent of the variance in plasma ACE activity is accounted for by the ACE insertion/deletion (I/D) polymorphism, the D allele being associated with higher activity. We therefore hypothesized that the presence of the D allele would be associated with the development of ARDS. Ninety-six white patients fulfilling American/European Consensus Committee criteria for ARDS were genotyped for the ACE polymorphism together with individuals from three comparison groups: 88 white patients with non-ARDS respiratory failure ventilated in the intensive care unit (ICU), 174 ICU patients undergoing coronary artery bypass grafting, and 1,906 individuals from a general population group. DD genotype frequency was increased in the patients with ARDS compared with the ICU (p = 0.00008), coronary artery bypass grafting (p = 0.0009), and general population group (p = 0.00004) control groups and was significantly associated with mortality in the ARDS group (p < 0.02). These data suggest a potential role for renin-angiotensin systems in the pathogenesis of ARDS and for the first time implicate genetic factors in the development and progression of this syndrome.