Pharmacogenomic studies of hypertension: paving the way for personalized antihypertensive treatment

Increasing clinical evidence supports the implementation of genotyping for anti-hypertensive drug dosing and selection. Despite robust evidence gleaned from clinical trials, the translation of genotype guided therapy into clinical practice faces significant challenges. Challenges to implementation include the small effect size of individual variants and the polygenetic nature of antihypertensive drug response, a lack of expert consensus on dosing guidelines even without genetic information, and proper definition of major antihypertensive drug toxicities. Balancing clinical benefit with cost, while overcoming these challenges, remains crucial.

This review presents the most impactful clinical trials and cohorts which continue to inform and guide future investigation. Variants were selected from among those identified in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR), the Genetic Epidemiology of Responses to Antihypertensives study (GERA), the Genetics of Drug Responsiveness in Essential Hypertension (GENRES) study, the SOPHIA study, the Milan Hypertension Pharmacogenomics of hydro-chlorothiazide (MIHYPHCTZ), the Campania Salute Network, the International Verapamil SR Trandolapril Study (INVEST), the Nordic Diltiazem (NORDIL) Study, GenHAT, and others.

The polygenic nature of antihypertensive drug response is a major barrier to clinical implementation. Further studies examining clinical effectiveness are required to support broad-based implementation of genotype-based prescribing in medical practice.