['Angiopoietin-2 (Ang-2) is a potent regulator of vascular permeability and inflammation in acute lung injury and acute respiratory distress syndrome (ARDS). Genetic variants in the Ang-2 gene may lead to altered activities of Ang-2 (or ANGPT2) gene. The aim of this study was to assess if genetic variants of Ang-2 are associated with the risk of ARDS.', 'Unmatched, case-control study nested within a prospectively enrolled cohort.', 'Intensive care units (ICU) of an academic medical center.', 'About 1,529 critically ill patients with risk factors for ARDS consecutively admitted to the ICUs from 1999 to 2006. Cases were 449 patients who developed ARDS and controls were 1,080 subjects who did not developed ARDS.', 'None.', 'Nine tagging SNPs (tSNPs) spanning the entire Ang-2 gene were genotyped in all patients. The results were analyzed using logistic regression models, adjusting for covariates. The variant T allele of one tSNP (rs2515475) was significantly associated with increased risk of ARDS (OR(adjusted) = 1.28; P = 0.042). This association was stronger in subjects with extrapulmonary injuries (OR(adjusted) = 1.79; P = 0.004). Haplotype TT in block 2 containing the T allele of the rs2515475 was also significantly associated with higher risk of ARDS (OR(adjusted) = 1.42; P = 0.009), particularly in subjects with extrapulmonary injuries (OR(adjusted) = 1.90; P = 0.004).'] Are genetic variants in the angiopoietin-2 gene associated with increased risk of ARDS?