Pankaj Arora
Pankaj Arora, M.D., M.D., professor of medicine in the Division of Cardiovascular Disease at the University of Alabama at Birmingham Marnix E. Heersink School of Medicine and director of the UAB Cardiovascular Genetics Clinic, has received a five-year R01 grant from the National Heart, Lung, and Blood Institute to investigate how genetic differences in natriuretic peptide levels influence blood pressure and an individual’s response to dietary salt.
The study addresses a fundamental question in hypertension: Why can the same amount of dietary salt have very different effects on blood pressure from one person to another?
“People can have very different blood pressure responses to the same amount of dietary salt,” Arora said. “We believe genetic differences in the natriuretic peptide system may help explain some of that variation. This study gives us an opportunity to identify those genetic factors and then determine how they affect human physiology.”
The project will combine large‑scale genomic discovery with a controlled clinical physiology study. Arora’s team will analyze genomic data from the NIH Trans-Omics for Precision Medicine Program, All of Us and the UK Biobank to identify genetic variants linked to natriuretic peptide levels. These findings will be used to develop a polygenic score estimating an individual’s genetically determined natriuretic peptide levels.
In the second part of the project, the team will enroll 200 adults with hypertension in a genotype-guided clinical study. Participants will be selected based on genetically predicted natriuretic peptide levels, with approximately half having a low polygenic score and half having a high polygenic score.
This genotype-first design is a key feature of the study. Rather than enrolling participants and examining their genetic profiles afterward, researchers will use genetic information to identify participants with different predicted levels of natriuretic peptide and then prospectively study how those individuals respond to changes in salt and volume.
“The long-term goal is to use genetic information to better understand cardiovascular biology and ultimately improve how we identify and treat people at risk,” Arora said.
By connecting population-scale genomic discovery with controlled human physiology, the study aims to move beyond simply identifying genetic associations and toward understanding how those genetic differences affect cardiovascular function. The findings could help establish a foundation for future precision-medicine approaches to hypertension and cardiovascular disease.