For some frequent flyers, air travel is always a bumpy ride, even when there is no turbulence. Dizziness, 'pins and needles,' headaches, and nausea are all symptoms of altitude sickness that can ruin a person’s flying experience. New research has uncovered inherited traits that explain why some people are more prone to illness at high altitudes.

Altitude or “mountain” sickness happens when a person’s body cannot absorb enough oxygen to satisfy its demands, which is a condition known as hypoxia. This occurs because oxygen molecules are more spread out at higher altitudes, and not because oxygen levels are lower, which is a common misconception. For most people, this only becomes a problem at heights over 8,000 feet, so most commercial flights maintain an artificial cabin pressure that mimics this elevation.

However, there are travelers who still can’t stomach these flights and succumb to altitude sickness no matter what. But why? To answer this question, geneticists at the University of Californin, San Diego turned to communities that live in lofty reaches of the Andes mountain ranges in South America.

Over 140 million people live at high elevations across the globe — from the plateaus of Ethiopia and China to the Rocky Mountains in the U.S. Over several generations, many have adapted by producing more hemoglobin, the protein that carries oxygen in the blood, but some people living in these areas never cope with the lower air density and suffer from chronic mountain sickness.

In search of genetic traits that might explain this disparity, the researchers compared the genomes of 10 normal residents of the Andes and 10 individuals with chronic mountain sickness.

They identified two genes, ANP32D and SENP1, that were more active in people with mountain sickness.

"While a number of published articles have described an association between certain genes and the ability for humans to withstand low oxygen at high levels, it was very hard to be sure if the association was causal," said senior author Dr. Gabriel Haddad, chair of the pediatrics department at UC San Diego.

To test for a possible causal link, the team collected skin cells from these subjects and deprived the cells of oxygen. Exposure to hypoxia boosted the production of ANP32D and SENP1 in the cells from people with chronic mountain sickness, but not in normal cells, suggesting that these two genes play a role in responding to oxygen.

Next, the researchers lowered the production of these two genes in fruit flies — a popular animal model. These mutated fruit flies were able to survive for longer stints under extreme hypoxia when compared to normal fruit flies.

"We found that flies with these genes down-regulated had a remarkably enhanced survival rate under hypoxia," concluded Haddad. "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."

Source: Zhou D, Udpa N, Ronen R, et al. Whole-Genome Sequencing Uncovers the Genetic Basis of Chronic Mountain Sickness in Andean Highlanders. American Journal of Human Genetics. 2013.