Researchers identify genetic root of mountain sickness

Exposure to low oxygen levels, such as those present at high altitudes, can wreak havoc on the body. Now researchers reporting August 15 in the American Journal of Human Genetics, published by Cell Press, have uncovered genes that play a role in causing this damage, making them attractive targets for treatments against chronic mountain sickness and other conditions that involve oxygen deprivation.

There are approximately140 million people living permanently at high altitudes, where oxygen levels are low. Many of them have adapted to their environment, but others have chronic mountain sickness—characterized by heart attacks, strokes, and pulmonary issues at an early age.

To identify and characterize the genes that are involved in adaptation to high-altitude, low-oxygen environments, scientists sequenced the entire genomes of 20 individuals living in the Andes—ten with chronic mountain sickness and ten without. The investigators discovered 11 regions with significant differences between the two groups. In these regions, two genes (a blood cell regulator, SENP1, and a cancer-associated gene, ANP32D) were expressed to a greater extent in individuals with chronic mountain sickness than in those without the condition in response to low oxygen levels.

The team also demonstrated that reducing the expression of these two genes improved survival under low-oxygen conditions both in flies and in human cells. "We showed that the genes that were identified by the whole-genome scan were actually linked causally to sickness in low-oxygen environments," explains co–senior author Dr. Gabriel Haddad of the University of California, San Diego.

Numerous clinical applications could result from the findings. "With further study, the two genes we identified and validated may become potential drug targets for treating conditions related to low oxygen levels, such as strokes and heart attacks. In addition, they may also be considered as targets for a potential drug treatment for chronic mountain sickness," says Dr. Haddad.

American Journal of Human Genetics, Zhou et al.: "Whole genome sequencing uncovers the genetic basis of chronic mountain sickness in Andean highlanders."