The association of angiotensin-converting enzyme gene insertion/deletion polymorphisms with adaptation to high altitude: A meta-analysis

J Renin Angiotensin Aldosterone Syst. 2016 Mar 23;17(1):1470320315627410. doi: 10.1177/1470320315627410. Print Jan-Mar 2016.


Background: Fluid retention is linked to the physiology and pathophysiology of humans at high altitude (HA). The angiotensin-converting enzyme (ACE) gene plays a role in the regulation of plasma volume and vascular tone.

Materials and methods: In this meta-analysis, eligible studies published before 1 September 2015 that focused on the association between the ACE insertion/deletion (I/D) polymorphism and HA adaption were identified by searching the PubMed, Web of Science, Embase and Medline online databases. We used a fixed-effects model and assessed the study qualities multiple times.

Results: The seven selected studies included a total of 582 HA-native individuals and 497 low-altitude controls, and these subjects were analyzed for the ACE I/D gene polymorphism. A significant association was found between the ACE DD genotype and HA maladaptation. The results for genotype DD versus ID + II were as follows: Odds ratio (OR) = 0.46; 95% CI 0.31-0.70; p = 0.0002. The results for genotype ID versus DD were as follows: OR = 1.97; 95% CI 1.27-3.06; p = 0.002.

Conclusions: Our findings suggested that the DD genotype of ACE is a risk factor for HA maladaptation and that the presence of fewer ACE DD allele carriers in a population indicates a greater ability of that population to adapt to HA.

Keywords: Adaptation; altitude; altitude disorders; altitude sickness; angiotensin-converting enzyme; deletion; genotype; high-altitude; hypoxia; insertion; meta-analysis; oxygen absorption; polymorphism.

Publication types

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

MeSH terms

  • Altitude*
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Humans
  • INDEL Mutation / genetics*
  • Mutagenesis, Insertional / genetics*
  • Peptidyl-Dipeptidase A / genetics*


  • ACE protein, human
  • Peptidyl-Dipeptidase A