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.
Center for Respiratory Research, Royal Free and University College, London Medical School, Rayne Institute, London, United Kingdom. richard.marshall@ucl.ac.uk
Richard P
RP
Marshall
Suzanne
S
Webb
Geoffrey J
GJ
Bellingan
Hugh E
HE
Montgomery
Babar
B
Chaudhari
Robin J
RJ
McAnulty
Steve E
SE
Humphries
Mike R
MR
Hill
Geoffrey J
GJ
Laurent
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015331:Cohort Studies; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D011336:Probability; D012016:Reference Values; D012128:Respiratory Distress Syndrome / Q000235:genetics* / Q000503:physiopathology*; D018570:Risk Assessment; D012680:Sensitivity and Specificity
D007703:Peptidyl-Dipeptidase A