Essential hypertension affects 25% of adults and constitutes a major risk factor for stroke, heart attack, heart failure, and kidney failure. About 50% percent of essential hypertension is thought to be hereditary. Determining the genetic cause of essential hypertension has been difficult because the level of blood pressure is the result of the interplay between heredity and environment. Diagnosis and early treatment of hypertension are important because hypertension-related diseases are the leading causes of morbidity and mortality in industrialized countries.
The researchers report that these gene variations, also called polymorphisms, either by themselves or through interaction with variations of other genes, are associated with hypertension in several populations: Caucasian American, Ghanaian, and Japanese. The presence of these gene variations can be determined by a simple genetic test developed by the researchers. This test assesses an individual’s risk of developing high blood pressure based on detection of inherited gene variations that encode for a protein called G protein coupled receptor kinase type 4 (GRK4). GRK4 variations are associated with an inability to normally eliminate sodium from the body.
“Patients with even a single GRK4 variation have a significant lifetime risk for developing hypertension,” said Pedro A. Jose, MD, PhD, professor of pediatrics and of physiology and biophysics at Georgetown, the senior author of the PNAS paper. “We have now identified the genetic abnormalities that cause this error and so we have a better idea of the impact of these gene variations in the development of hypertension in three distinct racial groups.”
“This discovery has led to a high quality test that should be suitable for screening a large number of patients based on a fluorescent molecular beacon assay and will aid physicians in their diagnosis of genetic forms of hypertension,” said Robin A. Felder, Ph.D., professor of pathology and director of the Medical Automation Research Center of the University of Virginia, the lead author on the paper. “The genetic information disclosed by the test will allow physicians to provide guidance to patients with a family history of hypertension who wish to know if they should modify their lifestyles to help prevent the debilitating consequences such as kidney failure, heart failure, stroke, blindness of high blood pressure,” said Dr. Jose and Dr. Felder.
Identification of this leading cause of hypertension should lead to improved medical treatments for the disease. The University of Virginia and Georgetown teams, in collaboration with Dr. Hironobu Sanada at Fukushima University in Japan, have also reported on the use of antisense technology to correct the biochemical error in human kidney cells that leads to the high blood pressure. The research teams have produced human kidney cell lines that may be useful in discovering other therapeutic methods to treat high blood pressure.
Dr. Felder and Dr. Jose submitted their discoveries for patent protection in January 1999. The resulting patents have been recently assigned to Hypogen Inc. in Charlottesville, Va. The research reported in PNAS was funded by the National Institutes of Health (National Heart Lung and Blood Institute, National Institute for Diabetes, Digestive, and Kidney Diseases and the National Center for Research Resources).
Georgetown University Medical Center includes the nationally ranked School of Medicine, School of Nursing and Health Studies, the Lombardi Cancer Center and a biomedical research enterprise. For more information, visit www.georgetown.edu/gumc.
Journal
Proceedings of the National Academy of Sciences