High blood pressure (HTN) is one of the leading causes of death in the world. However, the causes of high blood pressure are poorly understood. Rare genetic causes for HTN can give insights into the pathways causing HTN in other patients. One such disease is Gitelman syndrome, where patients have a defect in both copies of the gene SLC12A3, which codes for a protein, which in turn works as a salt transporter in the kidney.
Gitelman syndrome sufferers lose salt in their urine and have low blood pressure. In patients where the SLC12A3 protein is too active, we see high blood pressure in the disease Familial Hyperkalaemic Hypertension (FHHt). SLC12A3 therefore seems important in regulating blood pressure.
We plan a statistical study using a large database (UK Biobank) of 500,000 apparently healthy individuals to see if variations in their SLC12A3 genes are linked to HTN and associated diseases. Based on known frequencies of SLC12A3 defects, we expect that 5000-15000 of these patients will have an abnormality in at least one SLC12A3 gene (each person has two copies, one from each parent). We will study if this is associated with their blood pressure, heart rate, behaviour of their heart during exercise and appearance of their heart at rest (on MRI scanning). Our research group has already shown that Gitelman patients have a defective immune system; we will study if this is the case in people enrolled in the UK Biobank. We will also look at whether SLC12A3 variants affect bone strength (which is often increased in Gitelman syndrome). We will use the database to study other genes besides SLC12A3 which are known to affect blood pressure.
