Yale Researchers Identify Gene Mutations to High Blood Pressure


Researchers from Yale University have reported in the Feb. 11 issue of the journal Science the identification of two novel genetic mutations that can trigger hypertension in up to a third of patients suffering from primary essential hypertension.

The findings are a major step in understanding the causes of high blood pressure, which according to the Centers for Disease Control and Prevention (CDC) affects nearly one third of U.S. adults.

Richard Lifton, Sterling Professor and chair of the Department of Genetics, professor of internal medicine and senior author of the paper, said “These findings may lead to a genetic screening test for this common cause of severe hypertension.”

Aldosterone producing adrenal gland tumors (APA) or Conn’s Syndrome can be found in 5 to 10% of patients with severe hypertension. This form of hypertension is associated with low levels of potassium. Removing these tumors can cure this form of hypertension.

The researchers conducted “whole exome” sequencing of the APA tumors removed from patients and compared them with the patients' normal DNA. Analysis showed nine mutations, including two different variants in KCNJ5, a gene that codes for a potassium channel which moves potassium in and out of cells.

The investigators discovered that these mutations cause both aldosterone release and tumor formation by allowing the encoded protein, a potassium channel, to conduct sodium rather than only allowing potassium to pass through the channel.

In addition to causing these adrenal tumors, inherited mutations in the same gene were also found to be the cause of a rare familial form of severe hypertension.


The results underscore the value of whole exome sequencing, or decoding of all of a patient's genes rather than just a few suspect gene targets, said Lifton, who is an investigator for the Howard Hughes Medical Institute.

"This gene was not on anybody's list to sequence in an investigation of this disease," Lifton said. "We really hit the jackpot."

An ideal blood pressure is considered 120/80 mm Hg or lower for an adult over age 20.

A single high reading does not necessarily mean that you have high blood pressure. However, if readings stay at 140/90 mm Hg or above (systolic 140 or above OR diastolic 90 or above) over time, your doctor will likely want you to begin a treatment program.

If, while monitoring your blood pressure, you get a systolic reading of 180 mm Hg or higher OR a diastolic reading of 110 mm HG or higher, wait a couple of minutes and take it again. If the reading is still at or above that level, you should seek immediate emergency medical treatment.

Most people with high blood pressure have no signs or symptoms, even if blood pressure readings reach dangerously high levels.

Although a few people with early-stage high blood pressure may have dull headaches, dizzy spells or a few more nosebleeds than normal, these signs and symptoms typically don't occur until high blood pressure has reached a severe stage.

For more information on hypertension:
Medline Plus – Hypertension
American Heart Association -- Hypertension
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), 2004 (pdf)

Yale Office of Public Affairs press release, February 10, 2011
Choi M, et al. "K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension" Science 2011; 331: 768-772