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A Journal on Anesthesiology, Resuscitation, Analgesia and Intensive Care
Minerva Anestesiologica 2013 August;79(8):861-70
Effect of angiotensin converting enzyme gene I/D polymorphism and its expression on clinical outcome in acute respiratory distress syndrome
Tsantes A. E. 1, Kopterides P. 2, Bonovas S. 3, 4, 5, Bagos P. 4, Antonakos G. 6, Nikolopoulos G. K. 3, 7, Gialeraki A. 1, Kapsimali V. 8, Kyriakou E. 1, Kokori S. 1, Dima K. 6, Armaganidis A. 2, Tsangaris I. 2 ✉
1 Laboratory of Haematology and Blood Bank Unit, “Attiko” University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece;
2 Second Department of Critical Care Medicine, “Attiko” University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece;
3 Hellenic Centre for Disease Control and Prevention, Athens, Greece;
4 Department of Computer Science and Biomedical Informatics, University of Central Greece, Lamia, Greece;
5 Department of Pharmacology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece;
6 Department of Clinical Biochemistry, “Attiko” University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece;
7 National Development and Research Institutes, Inc. (IAS/NIDA Post-Doctoral Research Fellow), New York, NY, USA;
8 Department of Microbiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
Background: The role of the D allele of the angiotensin-converting enzyme (ACE) gene I/D polymorphism in the clinical outcomes of patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) remains controversial. Our aim was to assess simultaneously the effect of the ACE I/D polymorphisms as well as the serum and BALF ACE levels on prognosis of patients with ARDS.
Methods: Sixty-nine mechanically ventilated patients with ALI/ARDS were recruited. ACE activity levels both in serum and BALF were assessed by chemical methods. Patients were genotyped for ACE I/D polymorphisms. Time-to-event analysis evaluated the variables associated with the 28-day and 90-day mortality. Finally, we performed a meta-analysis of studies examining the association between ACE I/D polymorphisms and mortality of ALI/ARDS patients.
Results: In the multivariable model, age, lung compliance, serum lactate and serum ACE levels were significantly associated with both 28- and 90-day mortality. No significant correlation was found between serum and BALF ACE levels (Spearman’s rho=0.054; P=0.66). Serum ACE concentrations were significantly higher (P=0.046) in patients with D/D genotype versus the two other groups combined (I/D and I/I genotypes). The meta-analysis of 6 studies (including ours) provided evidence that D allele is significantly associated with increased mortality in ALI/ARDS patients, yielding a per-allele odds ratio of 1.76 (95% CI: 1.19, 2.59).
Conclusion: Serum ACE levels appear to be affected by the I/D polymorphism and are correlated with prognosis in patients with ALI/ARDS indicating that further investigation of the clinical significance of the ACE in ARDS might be of value.