Genetic variants associated with angiotensin-converting enzyme inhibitor-induced cough: a genome-wide association study in a Swedish population

Pharmacogenomics. 2017 Feb;18(3):201-213. doi: 10.2217/pgs-2016-0184. Epub 2017 Jan 13.


Aim: We conducted a genome-wide association study on angiotensin-converting enzyme inhibitor-induced cough and used our dataset to replicate candidate genes identified in previous studies.

Patients & methods: A total of 124 patients and 1345 treated controls were genotyped using Illumina arrays. The genome-wide significance level was set to p < 5 × 10-8.

Results: We identified nearly genome-wide significant associations in CLASP1, PDE11A, KCNMB2, TGFA, SLC38A6 and MMP16. The strongest association was with rs62151109 in CLASP1 (odds ratio: 3.97; p = 9.44 × 10-8). All top hits except two were located in intronic or noncoding DNA regions. None of the candidate genes were significantly associated in our study.

Conclusion: Angiotensin-converting enzyme inhibitor-induced cough is potentially associated with genes that are independent of bradykinin pathways.

Keywords: angiotensin converting enzyme inhibitors; bradykinin; cough; drug-related side effects and adverse reactions; enalapril; genome-wide association study; lisinopril; pharmacogenetics; quinapril; ramipril.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects*
  • Cough / chemically induced*
  • Cough / epidemiology
  • Cough / genetics*
  • Female
  • Genetic Association Studies / methods
  • Genetic Variation / genetics*
  • Genome-Wide Association Study / methods*
  • Humans
  • Male
  • Middle Aged
  • Population Surveillance* / methods
  • Surveys and Questionnaires
  • Sweden / epidemiology


  • Angiotensin-Converting Enzyme Inhibitors