Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with high-altitude pulmonary oedema: a meta-analysis

J Renin Angiotensin Aldosterone Syst. 2011 Dec;12(4):617-23. doi: 10.1177/1470320311406572. Epub 2011 Apr 27.


Background and objective: High-altitude pulmonary oedema (HAPE) is a non-cardiogenic hydrostatic oedema involving a genetic component. Considering the low incidence of HAPE, sample sizes in current reports are relatively limited. We aimed to assess the association between the angiotensin-converting enzyme (ACE) I/D polymorphism and HAPE via a meta-analysis of published and unpublished data.

Materials and methods: We searched PubMed, CBM, CNKI, and Cochrane Library Database before 20 November 2010. A random-effects model was applied (STATA) and study quality was assessed in duplicate.

Results: A total of five studies including 305 cases and 662 controls were meta-analysed. The summary odds ratio (OR) indicated that no significant differences in risk of developing HAPE were found between carriers of ACE D and I alleles (OR = 1.20; 95% confidence interval (CI), 0.98-1.48; p = 0.084). Lack of association persisted for genotypes under the recessive mode. However, genotype association under the dominant mode showed D allele carriers significantly conferred a 1.55-fold increased HAPE risk compared with II genotype carriers (95% CI, 1.15-2.08; p = 0.004). Funnel plot and Egger's test suggested no evidence of publication bias.

Conclusions: Our results supported the notion that ACE D allele carriers were at significant increased risk of developing HAPE.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Altitude
  • Altitude Sickness / enzymology*
  • Altitude Sickness / genetics*
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Humans
  • Hypertension, Pulmonary / enzymology*
  • Hypertension, Pulmonary / genetics*
  • INDEL Mutation / genetics*
  • Peptidyl-Dipeptidase A / genetics*
  • Polymorphism, Genetic*
  • Publication Bias


  • ACE protein, human
  • Peptidyl-Dipeptidase A

Supplementary concepts

  • Pulmonary edema of mountaineers