Genetic differences and aberrant methylation in the apelin system predict the risk of high-altitude pulmonary edema

Significance Exposure to a high-altitude (HA) hypobaric hypoxia environment produces physiological changes. Among these, the changes in the apelin signaling system are significant because this system regulates vascular and oxygen homeostasis. This study demonstrates that the HA environment stimulates the apelin system to distinguish genetic variants and the methylation profile of CpG islands that may impair or improve pulmonary vascular function, thereby resulting in HA pulmonary edema (HAPE) in patients or adaptation in healthy controls. Of the several variants of this system,apelin rs3761581G and rs2235312T , individually and in combination, and a greater methylation of a CpG island in the 5′ UTR, associated with low levels of apelin-13 and nitrite in HAPE, whereas a reverse trend was observed in the control groups.