ArticleProceedings of the National Academy of Sciences of the United States of America2024
Genetic polymorphisms and expression of Rhesus blood group RHCE are associated with 2,3-bisphosphoglycerate in humans at high altitude.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 26 citations in OpenAlex.
- Blood-storage duration affects hematological and metabolic profiles in patients with sickle cell disease receiving transfusions.The Journal of clinical investigation · 2025Trial
- Functional and multi-omics signatures of mitapivat efficacy upon activation of pyruvate kinase in red blood cells from patients with sickle cell disease.Haematologica · 2024Trial
- Lower efficacy of transfusion of red blood cells from donors with sickle cell trait.HemaSphere · 2026Article
- Red blood cells serve as a primary glucose sink to improve glucose tolerance at altitude.Cell metabolism · 2026Article
- Caffeine impairs red blood cell storage quality by dual inhibition of ADORA2b signaling and G6PD activity.Haematologica · 2026Article
- High-Throughput Metabolomics in Transfusion Medicine.Methods in molecular biology (Clifton, N.J.) · 2026Article
- GPX4 regulates lipid peroxidation and ferroptosis of stored red blood cells.Blood red cells & iron · 2025Article
- Metabolic alterations in erythrocytes associated with long-term hypoxia at high altitude.BMC genomics · 2025Article
- From metabolomics to transfusion-associated immunomodulation.Current opinion in immunology · 2025Review
- Increased Exercise Tolerance in G6PD African Variant Mice Driven by Metabolic Adaptations and Erythrophagocytosis.Antioxidants (Basel, Switzerland) · 2025Article
- Altered branched chain ketoacids underlie shared metabolic phenotypes in type 1 diabetes and maple syrup urine disease.Communications medicine · 2025Article
- Red blood cell metabolism: a window on systems health towards clinical metabolomics.Current opinion in hematology · 2025Review
- Article
- Increased exercise tolerance in humanized G6PD-deficient mice.Blood advances · 2025Article
- Assessing the kinetics of oxygen-unloading from red cells using FlowScore, a flow-cytometric proxy of the functional quality of blood.EBioMedicine · 2025Article
- Metabolic insights into hypoxia adaptation in adolescent athletes at different altitudes: a cross-sectional study.Frontiers in molecular biosciences · 2025Article
- It's in your blood: The impact of age, sex, genetic factors and exposures on stored red blood cell metabolism.Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis · 2024Review
- An intronic polymorphism associated with 2,3-bisphosphoglycerate levels in human red cells is linked to expression of RhCE blood groups.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Reply to McGowan et al.: An intronic polymorphism associated with 2,3-bisphosphoglycerate levels in human red blood cells is linked to expression of RhCE blood groups.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 10 institutions in 6 countries.
Funding
Abstract
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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.