Association between genetic polymorphisms and angiotensin-converting enzyme inhibitor-induced cough: a systematic review and meta-analysis

Pharmacogenomics. 2019 Feb;20(3):189-212. doi: 10.2217/pgs-2018-0157. Epub 2019 Jan 23.


Aim: Genetic polymorphisms may influence the incidence of angiotensin-converting enzyme (ACE) inhibitor-induced cough. This study aims to investigate this association.

Methods: Ten electronic databases and PharmGKB were systematically searched. Pooled odds ratio values and their 95% CI were used to assess the association, using the random-effects model.

Results: A total of 26 studies were included in the review, 17 of them were included from two separated meta-analysis (ACE I/D or BDKRB2-58T/C). Significant association was found between ACE I/D I carriers (ACE gene insertion) and ACE inhibitor-induced cough, showing racial and age differences.

Conclusion: This study demonstrated that ACE I/D but not BDKRB2-58T/C polymorphism could be a predictor for the risk of ACE inhibitor-induced cough, especially in east Asians and the aged.

Keywords: ACE inhibitor; cough; genetic polymorphism.

Publication types

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

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Asian People / genetics
  • Cough / chemically induced
  • Cough / drug therapy
  • Cough / genetics*
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Hypertension / genetics
  • Polymorphism, Genetic


  • Angiotensin-Converting Enzyme Inhibitors