The Genetics of Altitude Tolerance The Evidence for Inherited Susceptibility to Acute Mountain Sickness

Objective: Acute mountain sickness (AMS) has become a significant environmental health issue as improvements in transportation, "environmental tourism," and resource development lure more people to the highlands. Whether there is a genetic contribution to AMS susceptibility is a central question in high-altitude medicine. This article provides a systematic review of the evidence supporting such an innate predisposition. Methods: Scientific literature databases were screened using the terms "acute mountain sickness/AMS" and "altitude illness" combined with the terms "DNA," "gene," "genetic," or "polymorphism." Results: Sixteen genes from a variety of pathways have been tested for association with AMS and variants in eight showed positive associations suggesting that AMS is an environmentally mediated polygenic disorder. Conclusions: The data suggest that genotype contributes to capacity to rapidly and efficiently acclimatize to altitude; nevertheless, the mechanisms by which this occurs have yet to be elucidated.