Genetic polymorphisms and expression of Rhesus blood group RHCE are associated with 2,3-bisphosphoglycerate in humans at high altitude - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2023

Genetic polymorphisms and expression of Rhesus blood group RHCE are associated with 2,3-bisphosphoglycerate in humans at high altitude

Angelo D’alessandro
Eric Earley
Travis Nemkov
Daniel Stephenson
  • Fonction : Auteur
Monika Dzieciatkowska
Kirk Hansen
  • Fonction : Auteur
Giampaolo Minetti
Benoit Champigneulle
Emeric Stauffer
  • Fonction : Auteur
Aurélien Pichon
  • Fonction : Auteur
Michael Furian
  • Fonction : Auteur
Steven Kleinman
Philip Norris
  • Fonction : Auteur
Michael Busch
Grier Page
Lars Kaestner

Résumé

Red blood cell (RBC) metabolic reprogramming upon exposure to high altitude contributes to physiological human adaptations to hypoxia, a multifaceted process critical to health and disease. To delve into the molecular underpinnings of this phenomenon, first, we performed a multi-omics analysis of RBCs from six lowlanders after exposure to high-altitude hypoxia, with longitudinal sampling at baseline, upon ascent to 5,100 m and descent to sea level. Results highlighted an association between erythrocyte levels of 2,3-bisphosphoglycerate (BPG), an allosteric regulator of hemoglobin that favors oxygen off-loading in the face of hypoxia, and expression levels of the Rhesus blood group RHCE protein. We then expanded on these findings by measuring BPG in RBCs from 13,091 blood donors from the Recipient Epidemiology and Donor Evaluation Study. These data informed a genome-wide association study using BPG levels as a quantitative trait, which identified genetic polymorphisms in the region coding for the Rhesus blood group RHCE as critical determinants of BPG levels in erythrocytes from healthy human volunteers. Mechanistically, we suggest that the Rh group complex, which participates in the exchange of ammonium with the extracellular compartment, may contribute to intracellular alkalinization, thus favoring BPG mutase activity.

Dates et versions

hal-04511897 , version 1 (19-03-2024)

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Citer

Angelo D’alessandro, Eric Earley, Travis Nemkov, Daniel Stephenson, Monika Dzieciatkowska, et al.. Genetic polymorphisms and expression of Rhesus blood group RHCE are associated with 2,3-bisphosphoglycerate in humans at high altitude. Proceedings of the National Academy of Sciences of the United States of America, 2023, 121 (1), ⟨10.1073/pnas.2315930120⟩. ⟨hal-04511897⟩

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