Gene which helps people cope with low oxygen levels at high altitudes could become target for new drugs to treat heart disease

A gene thought to be involved in helping people to cope with low levels of oxygen when they live at high altitudes could become a target for new drugs to treat heart disease at low altitude, scientists have found.

Variants of the gene found in the genome of Ethiopians who live most of their lives several thousand feet above sea level are believed to play a key role in helping people overcome the problems linked with low-oxygen concentrations when living at high-altitudes.

Now researchers have found that laboratory mice with low-level variants of the endothelin receptor type B (EDNRB) gene perform better than ordinary mice when subjected to low concentrations of oxygen – which could also help to explain why East Africans tend to be good at endurance sports such as long-distance running.

“This is the first demonstration that a gene involved in high-altitude adaptation is critical in protecting cardiac function in moderate to severe hypoxia [low oxygen] at sea level,” said Gabriel Haddad of the University of California San Diego.

“In addition to improving the health of the more than 140 million people living above 8,000 feet, information on how Ethiopians have adapted to high-altitude life might help us develop new and better therapies for low oxygen-related diseases at sea level – heart attack and stroke, for example,” said Dr Haddad.

The study found that mice with low-EDNRB, a protein that helps blood vessels to dilate and cells to proliferate during development, where still able to maintain healthy delivery of oxygen to their cells even when concentrations fell to 5 per cent – equivalent to breathing air on Mount Everest.

In contrast, normal mice suffered a 40 to 50 per cent drop in cardiac output. They were unable to maintain normal blood pressure and none of them survived to finish the experiment, according to the findings published in the journal Proceedings of the National Academy of Sciences.

“Lowering EDNRB does wonders for mice when environmental oxygen levels are low, leading us to conclude that the EDNRB gene plays a key role in human adaptation to low oxygen and high altitude,” Dr Haddad said.

Tsering Stobdan, a co-author of the study at San Diego, said: “The idea that reducing the expression of functional EDNRB to help cells and tissues endure extreme hypoxia is appealing and may lead to novel therapies for cardiac failure in the near future.”