biostudies-literatureBhattacharya SRegional Centre for BiotechnologyBaylor College of MedicineDepartment of Biotechnology, Ministry of Science and Technology, India103418https://www.ebi.ac.uk/biostudies/studies/S-EPMC8190441biostudies-literatureUnknown68<h4>Background</h4>We have previously described an evolutionarily selected Tibetan prolyl hydroxylase-2 (PHD2^D4E;C127S) variant that degrades the hypoxia-inducible factor (HIFα) more efficiently and protects these highlanders from hypoxia-triggered elevation in haemoglobin concentration. High altitude is known to cause acute mountain sickness (AMS) and high-altitude pulmonary edema (HAPE) in a section of rapidly ascending non-acclimatised lowlanders. These morbidities are often accompanied by inflammatory response and exposure to hypobaric hypoxia is presumed to be the principal causative agent. We have investigated whether PHD2^D4E;C127S variant is associated with prevention of hypoxia-mediated inflammatory milieu in Tibetan highlanders and therefore identify a potentEBioMedicineGain-of-function Tibetan PHD2^D4E;C127S variant suppresses monocyte function: A lesson in inflammatory response to inspired hypoxia.PMC8190441BT/PR22985Shrimali NMMohammad GGuchhait PBhattacharya SKoul PAPrchal JTfalseGain-of-function Tibetan PHD2^D4E;C127S variant suppresses monocyte function: A lesson in inflammatory response to inspired hypoxia.<h4>Background</h4>We have previously described an evolutionarily selected Tibetan prolyl hydroxylase-2 (PHD2^D4E;C127S) variant that degrades the hypoxia-inducible factor (HIFα) more efficiently and protects these highlanders from hypoxia-triggered elevation in haemoglobin concentration. High altitude is known to cause acute mountain sickness (AMS) and high-altitude pulmonary edema (HAPE) in a section of rapidly ascending non-acclimatised lowlanders. These morbidities are often accompanied by inflammatory response and exposure to hypobaric hypoxia is presumed to be the principal causative agent. We have investigated whether PHD2^D4E;C127S variant is associated with prevention of hypoxia-mediated inflammatory milieu in Tibetan highlanders and therefore identify a potent2021-01-01T00:00:00Z2021 Jun2026-05-08T23:09:09.958Z2022-02-10T15:20:23.16ZS-EPMC81904413410239610.1016/j.ebiom.2021.103418