Hypertension precision medicine: the promise and pitfalls of pharmacogenomics

Abstract

Pharmacogenomics (PGx) has the potential to revolutionize hypertension management by tailoring antihypertensive therapy based on genetic profiles. Despite significant advances in genomic research, the clinical translation of PGx in hypertension remains challenging due to genetic complexity, variability in drug response, and implementation barriers. This review explores the genetic basis of hypertension, highlighting key pharmacogenomic markers that influence antihypertensive metabolism and efficacy, including CYP2D6, CYP3A4, UMOD, and ACE polymorphisms. We also examine the role of Mendelian randomization, polygenic risk scores in drug development and stratifying hypertension treatment response. While PGx offers opportunities for personalized medicine - such as reducing trial-and-error prescribing and improving adherence - several obstacles hinder its widespread adoption. These include limited clinical actionability, lack of large-scale randomized controlled trials, cost constraints, and concerns about equity and accessibility. Furthermore, drug-gene interactions and phenoconversion add complexity to implementation. Emerging technologies, including artificial intelligence-driven prescribing, microbiome integration, and pharmacoepigenomics, may enhance PGx precision in hypertension management. However, further research, clinical validation, and policy frameworks are necessary before PGx can be routinely incorporated into hypertension care. This review critically evaluates both the promise and limitations of PGx in hypertension, offering insights into the future of precision medicine in cardiovascular health.

Keywords: Hypertension; Mendelian randomization; artificial intelligence; drug interactions; pharmacogenomics; polygenic risk score; precision medicine.