Genetic Architecture of Natriuretic Peptides and Blood Pressure Response
University of Alabama at Birmingham
Summary
Natriuretic peptides (NPs) are hormones produced by the heart and play an important role in maintaining cardiovascular health and have favorable metabolic benefits. Low NP levels are associated with an increased likelihood of the development of cardiometabolic diseases like diabetes and hypertension. NP levels are known to be highly heritable, with up to half of the differences in NP levels being explained by genetics. The investigators aim to describe the genetic architecture of NPs by examining the genetic variants associated with NPs, and generate and validate a polygenic score (PGS) for NPs. The investigators will use this NP PGS to examine the association of genetically determined NP levels with cardiometabolic and cardiovascular outcomes. The investigators will conduct a genotype-guided physiological clinical trial that aims to assess the genetic factors affecting NP levels and their impact on blood pressure and NP response to saline infusion, high-salt diet, and low-salt diet. These findings will help support personal medicine approaches to lower the increasing burden of hypertension in the United States.
Description
NPs are vital cardiac-derived hormones that are known for their role in salt regulation, vascular function, and blood pressure (BP) regulation. NPs are also key regulators of insulin sensitivity, lipid metabolism, and energy expenditure. Recent evidence has shown that low NP levels are associated with higher risk of cardiometabolic diseases like hypertension (HTN). Animal studies have shown that the loss of the NP gene in mice is associated with the development of salt-sensitive HTN. Prior research indicates that individuals with genetically lower NP levels show higher systolic and diastolic B…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: * Age more than or equal to 18 years * Consenting to collection of genetic material and willing to adhere to study protocol * Stage I/II Hypertension (Systolic blood pressure: 130-159 and Diastolic blood pressure: 80-99 mm Hg) Exclusion Criteria: * Body mass index (BMI) more than 45 kg/m2 * History of uncontrolled hypertension (i.e., Systolic blood pressure more than or equal to 160 mmHg and/or Diastolic blood pressure more than or equal to 100 mmHg) * If taking more than or equal to 2 blood pressure medications at the time of screening * Systolic blood pressure more tha…
Interventions
- Dietary SupplementLow Salt Diet
8 days of diet with low salt content will be given to the study participants
- Dietary SupplementHigh Salt Diet
8 days of diet with high salt content will be given to the study participants
- Dietary SupplementSaline Infusion
2 Liters of normal saline infusion (0.25 ml/kg/min over 2 hours) will be given to the study participants at the end of each study period
Location
- University of Alabama at BirminghamBirmingham, Alabama