Genetic polymorphisms influencing antihypertensive drug responses

Br J Pharmacol. 2025 Feb;182(4):929-950. doi: 10.1111/bph.17414. Epub 2024 Dec 3.

Abstract

Hypertension is a major contributor to cardiovascular disease and its associated morbidity and mortality. The low efficacy observed with some anti-hypertensive therapies has been attributed partly to inter-individual genetic variability. This paper reviews the major findings regarding these genetic variabilities that modulate responses to anti-hypertensive therapies such as angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), diuretics, calcium channel blockers (CCBs) and β-adrenoceptor blockers. The importance of studying these genetic polymorphisms stems from the goal to optimise anti-hypertensive therapy for each individual patient, aiming for the highest efficacy and lowest risk of adverse effects. It is important to recognise that environmental and epigenetic factors can contribute to the observed variations in drug responses. Owing to the multigenic and multifactorial nature of drug responses, further research is crucial for translating these findings into clinical practice and the establishment of reliable recommendations.

Keywords: ACE inhibitors; angiotensin receptor blockers; calcium channel blockers; cardiovascular disease; diuretics; hypertension; pharmacogenomics; β‐adrenoceptor blockers.

Publication types

  • Review

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Angiotensin Receptor Antagonists / adverse effects
  • Angiotensin Receptor Antagonists / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Animals
  • Antihypertensive Agents* / pharmacology
  • Antihypertensive Agents* / therapeutic use
  • Calcium Channel Blockers / pharmacology
  • Calcium Channel Blockers / therapeutic use
  • Diuretics / pharmacology
  • Humans
  • Hypertension* / drug therapy
  • Hypertension* / genetics
  • Polymorphism, Genetic*

Substances

  • Antihypertensive Agents
  • Angiotensin-Converting Enzyme Inhibitors
  • Angiotensin Receptor Antagonists
  • Calcium Channel Blockers
  • Adrenergic beta-Antagonists
  • Diuretics