The genetics of altitude tolerance: the evidence for inherited susceptibility to acute mountain sickness.

Abstract

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. Scientific literature databases were screened using the terms "acute mountain sickness/AMS" and "altitude illness" combined with the terms "DNA," "gene," "genetic," or "polymorphism." 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. 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.