Cough associated with angiotensin-converting enzyme inhibitors: the role of pharmacogenetics
Year: 2025
Type: article
Abstract: Cough is a common side effect of angiotensin-converting enzyme (ACE) inhibitors, requiring the discontinuation of these medications. The frequency of dry cough in patients treated with ace inhibitors was approximately 1.5–11%, according to a previous study of 35%. The exact mechanism underlying cough caused by ACE inhibitors remains unclear, with the bradykinin pathway being the most widely accepted theory. The roles of genetic polymorphisms in enzyme proteins and ACE inhibitors have been actively discussed by the medical community. Thus, the first studies to assess the role of genetic factors focused on the polymorphism of the ACE (I/D) gene and different loci of the bradykinin B2 (BDKRB2) receptor gene. Subsequently, several meta-analyses of studies confirmed the relationship between the polymorphism of the ACE I/D gene (rs4646994) and the bradykinin B2 58T/C receptor gene (rs1799722). Other genes at potential risk of developing ACE inhibitors may encode transporter proteins that affect plasma ACE inhibitors or membrane transport proteins such as ABO and SCLO1B1 (OATP1B1), whose polymorphism is associated with cough. Genome-wide association studies (GWAS) searched for new candidate genes responsible for the development of cough caused by ACE inhibitors, and links were found with gene polymorphisms CLASP1, KCNIP4, PREP, NTSR1, L3MBTL4, SRBT1, PNPT1, and PCGF3, among which many genes are responsible for the neurobiological mechanisms of cough development. The results of pharmacogenomics studies have expanded the understanding of the pathophysiological processes underlying ACE-associated cough. According to the results of the GWAS studies, a polygenic prognosis of the risk of developing cough and discontinuation of ace inhibitors is possible, which in the future may identify patients at risk of developing ace-associated cough.
Author: M. V. Leonova
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4408219228