Raised HIF1α during normoxia in high altitude pulmonary edema susceptible non-mountaineers

High altitude pulmonary edema (HAPE) susceptibility is associated with EGLN1 polymorphisms, we hypothesized that HAPE-susceptible (HAPE-S, had HAPE episode in past) subjects may exhibit abnormal HIF1 alpha levels in normoxic conditions. We measured HIF1 alpha levels in HAPE-S and HAPE resistant (HAPE-R, no HAPE episode) individuals with similar pulmonary functions. Hemodynamic responses were also measured before and after normobaric hypoxia (Fi02 = 0.12 for 30 min duration at sea level) in both groups.. HIF1 alpha was higher in HAPE-S (320.3 +/- 267.5 vs 58.75 +/- 33.88 pg/ml, P < 0.05) than HAPE-R, at baseline, despite no significant difference in baseline oxygen saturations (97.7 +/- 1.7% and 98.8 +/- 0.7). As expected, HAPE-S showed an exaggerated increase in pulmonary artery pressure (27.9 +/- 6 vs 19.3 +/- 3.7 mm Hg, P < 0.05) and a fall in peripheral oxygen saturation (66.9 +/- 11.7 vs 78.7 +/- 3.8%, P < 0.05), when exposed to hypoxia. HIF1 alpha levels at baseline could accurately classify members of the two groups (AUC = 0.87). In a subset of the groups where hemoglobin fractions were additionally measured to understand the cause of elevated hypoxic response at baseline, two of four HAPE-S subjects showed reduced HbA. In conclusion, HIF 1 alpha levels during normoxia may represent an important marker for determination of HAPE susceptibility.