Genetic variations help predict risk for salt-induced high blood pressure

Researchers led by UVa Health System pathologist Robin Felder, Ph.D., have demonstrated that looking for several variations of genes that control blood pressure can predict the risk for high blood pressure caused by high levels of salt.

Once it is fully developed, this effective diagnostic test will be the first of its kind, says Dr. Felder, whose work will be published in the Feb. 23 issue of the journal Clinical Chemistry. When a subject had three or more variations in these genes, the new genetic test correctly predicted risk for salt-induced high blood pressure in 94 percent of cases. Health is adversely affected by high salt intake in up to half of Americans.

In a separate finding, two genes at most were necessary to predict with a 78 percent accuracy which people with high blood pressure (hypertension) had a low renin levels, a substance that is currently measured to help establish the diagnosis of salt (sodium chloride) sensitivity. Thus, the researchers found different genetic bases for low renin in the blood and for salt sensitivity. Salt sensitivity is defined as a greater than 10 percent increase in blood pressure following a high-salt meal.

The researchers also determined that the increase in subjects' blood pressure and inability to eliminate excess salt from their systems was directly related to how many variations were found in the participants' salt regulating genes, a phenomenon called a gene dosing effect. The more gene variants, the bigger the health problems.

"A genetic test for high blood pressure and/or salt sensitivity will be instrumental in motivating Americans to adopt heart healthy lifestyles and help to improve their overall health and quality of life," Dr. Felder said. "In addition, because the treatment of hypertension costs the U.S. health system more than $13 billion per year, this test could result in significant cost savings as well."

"Diagnostic genetic tests with this high level of predictive value for hypertension simply don't exist at this time," said Dr. Hironobu Sanada, M.D., Ph.D., Fukushima Medical University, who led the clinical trials of the diagnostic genetic panel with Japanese subjects. Dr. Sanada is a former UVa pathology fellow who studied and worked with Dr. Felder.

Performing extended studies among people with different ethnic origins, the research group hopes to demonstrate the effectiveness of this test in particular among African Americans, who have a higher incidence of salt-sensitive hypertension than other races. While 98 million Americans suffer from either high blood pressure or sensitivity to dietary salt (or both), until now no genetic test had been created that could predict who may develop these diseases. Salt sensitivity, with or without high blood pressure, has the same deleterious consequences as high blood pressure. Left undiagnosed, high blood pressure and/or salt sensitivity can lead to devastating consequences such as stroke, blindness, heart attack and kidney failure.