Genetic discoveries may help patients find the right blood pressure medication faster

A large international study led by FIMM researchers has identified genetic factors that influence how people tolerate common blood pressure medications. The study highlights how genetic variants enriched in the Finnish population can reveal biological insights that may remain hidden in larger but more genetically diverse populations.

High blood pressure affects more than a billion people worldwide and is one of the leading causes of heart disease and stroke. While several effective medications are available, many patients struggle to find a treatment that suits them. Up to half of patients stop or switch their blood pressure medication within the first year.

To understand why some patients tolerate these medications better than others, researchers analyzed genetic and health data from more than 400,000 blood pressure medication users in FinnGen, the UK Biobank and the Estonian Biobank.

Clues to the mystery of ACE inhibitor cough

One of the study’s most striking findings was a genetic variant in a gene called NTSR1 that protects against the persistent dry cough often caused by ACE inhibitors. The variant is found in around 3% of Finns but is extremely rare in most other populations. 

NTSR1 helps cells respond to a signaling molecule known as neurotensin. For decades, scientists have mainly explained ACE inhibitor-related cough through the accumulation of signaling molecules called bradykinin and substance P. The new findings suggest that neurotensin should also be considered part of the biological pathway behind this common side effect. 

“Large genetic studies infamously struggle to pinpoint the biological mechanisms behind associations. Utilizing the extensive health and genetic data collected through FinnGen, we found unusually convincing genetic evidence for the role of neurotensin in ACE inhibitor-induced cough,” says Felix Vaura, the study’s lead author from the Institute for Molecular Medicine Finland (FIMM) at the University of Helsinki.

“While it is still too early to draw definitive conclusions, previous receptor signaling and animal studies suggest that this unique Finnish mutation may provide a window into broader biological processes, including pain signaling.” 

Professor Samuli Ripatti, the corresponding author of the study, highlights the broader significance of the finding:
“Blood pressure medications are among the most prescribed drugs in Europe, and one third of ACE inhibitor users suffer from persistent cough. Our discovery points to a specific mechanism helping with this common adverse reaction.”

A drug-metabolism gene predicts intolerance to blood pressure medication

The researchers also identified a genetic variant in a gene called CYP3A4, which produces one of the body's most important drug-metabolizing enzymes. People carrying a specific variant known as CYP3A4*22 were more likely to switch away from calcium channel blockers, another major class of blood pressure medications.

While the variant is already known to affect how quickly certain medicines are broken down in the body, this is the first study to show that it also influences how well patients tolerate blood pressure treatment in a real-world setting.
The findings move the field a step closer to more personalized treatment of hypertension, where medication choices could be guided by a patient's genetic profile.

“We still mostly rely on trial and error to find the correct combination of blood pressure medications for each patient,” says Vaura. 
“Our findings show that genetics can influence whether a person tolerates commonly prescribed blood pressure medicines. Most patients would rather avoid trying several medications before finding the right one. In the future, genetic information could help doctors choose the most suitable treatment faster and make hypertension care more personalized.”

Original publication: Side effects in hypertension treatment: a pharmacogenomic analysis. Vaura F, Krebs K, Kiiskinen T, Rämö J, Tamlander M; Estonian Biobank research team; Rubinacci S, Milani L, Ripatti S.Eur Heart J. 2026 Aug 3:ehag575. doi: 10.1093/eurheartj/ehag575.