Genetics And Hypertension
Mutations in The Renin-Angiotensin System Affect Blood Pressure
Mar 7, 2008
Hypertension, or high blood pressure, is diagnosed when a person has consistent blood pressure readings of 140/90 mmHg or higher. When the increase in blood pressure is not due to another disease, such as kidney disorders, it is referred to as essential hypertension and is 90-95% of all hypertensive cases. Essential hypertension itself is compatible with living a long life, but it has the potential to cause complications in the presence of other factors, which can become life threatening.
Complications of chronically high blood pressure include aneurysm, stroke, kidney disease or renal failure, and weakening of the blood vessels in a process called arteriosclerosis. Standard prevention and treatment include reducing sodium intake, exercising for weight maintenance and to reduce obesity, cessation of smoking, and the use of diuretics to reduce water retention.
A family history of hypertension increases the risk of a person developing it themselves. This is because of the contribution of genetics to the development of the disease. It is generally accepted that genetics and the environment contribute evenly to hypertension. High sodium intake, obesity, high cholesterol, smoking, and a lack of physical activity are all environmental factors that may contribute to blood pressure increases. Genetic factors are inherited, or spontatneous, mutations in the proteins that help regulate blood pressure.
Blood Pressure Regulation
Blood pressure is regulated by the renin-angiotensin system (RAS). The liver, and often fat tissue, produces the protein angiotensinogen. This is cut by the enzyme renin into angiotensin I (Ang I). Angiotensin I is then cut by angiotensin converting enzyme (ACE) into angiotensin II (Ang II). Angiotensin II is the active protein, or peptide, in the system. It binds to its specific receptor on the surface of cells in the adrenal gland, kidney, liver, heart, brain, and blood vessels. There are several types of Ang II receptors, but the one important in blood pressure regulation is the angiotensin II type 1 receptor (AT1R).
Genetic Contributions to Hypertension
Severe mutations, including the deletion of entire portions of DNA within the gene for one of the proteins, often result in the development of hypertension at a young age. Subtle mutations in a single or a few bases of the genetic code, which are inherited over generations, take decades to manifest into a disorder. Over time, incremental increases in blood pressure due to the production of extra proteins or receptors will weaken the body’s feedback system that normally keeps any such aberrations in check. Eventually hypertension develops.
Hypertension is known as a polygenic, multifactorial disease. There is not one single mutation or one single gene that contributes to hypertension just as there is not one single environmental factor. This means that genetic screening to determine one’s risk for the disease is a far off possibility. There are several genes with several mutations each that have been identified as candidates. These include AGT, AT1R, REN (the gene for renin), and ACE, which are also drug targets for treating hypertension pharmaceutically. Some environmental factors influence different mutations to a greater extent.
Reference
Prater, Alicia M. "The Role of Single Nucleotide Polymorphisms in the Angiotensin II Type 1 Receptor Gene in Hypertension" (Dissertation) New York Medical College GSBMS, Dept of Pathology, 2007.
