Genetic Determinants of Hypertension
High blood pressure is a condition that affects a large part of our population and is a key risk factor for cardiovascular mortality. The incidence of high blood pressure increases with age. About 50% of people with high blood pressure are salt sensitive, which means that blood pressure goes up with high salt consumption and drops when salt in the diet is restricted. There is a large body of evidence to support the strong contribution of our genetic make-up to salt sensitivity.
Our database includes phenotypic characteristics and genotypic data for markers all along the genome of 605 individuals. Individuals were recruited at the Ottawa Heart Institute at the Hypertension clinic lead by Dr. Leenen as well as in Warsaw (Poland) by the Hypertension clinic lead by Dr. Januszewicz. Samples were genotyped at 526,549 positions in the genome at the University of Ottawa Heart Institute.Overall Objectives:
- We use whole-genome and whole-exome approaches to identifying genetic variants associated with salt-sensitive hypertension. Candidate genes have been selected based on genetic association and pathophysiological considerations. We have identified and continue to identify specific genetic make-up in these genes that are more frequent in salt sensitive individuals.
- We also aim to search the entire genome for chromosomal regions that are associated with salt-sensitivity. This unbiased approach might result in determination of new molecular pathways involved in blood pressure regulation.
Among environmental determinants, dietary sodium intake is the most important risk factor for the development of hypertension and is an independent risk factor for heart disease and stroke especially, after the age of 50. The clinical assessment of salt-sensitivity is currently unsustainable mainly because it is not safe for the patients who undergo a heavy dietary salt challenge intervention. Being able to accurately and rapidly identify genetically vulnerable individuals has potential applications in personalized medicine. A patient diagnosed with salt-sensitive hypertension would benefit not only from an appropriate diet, but also from tailored and appropriate drug treatment to maximize the likelihood of therapeutic efficacy, possibly reducing drug dosage and side effects. Similarly, hypertensive individuals diagnosed as non-salt sensitive may benefit from an appropriate medication target against other pathophysiological pathways. On the other hand, these studies should bring new mechanistic insights into the pathophysiology of salt-sensitive hypertension, which in turn may influence not only cardiovascular risk assessment and clinical management of patients, but also help identifying novel therapeutic targets.