Biological and genetic determinants of glycolysis: Phosphofructokinase isoforms boost energy status of stored red blood cells and transfusion outcomes.
Level 3 - non-randomized controlled study
Multi-cohort observational genetic and metabolomic association study linked with patient transfusion outcomes
PubMed 38964323 · doi:10.1016/j.cmet.2024.06.007
What was done
Researchers analyzed end-of-storage red blood cell (RBC) glycolytic metabolites in 13,029 blood donors from the Recipient Epidemiology and Donor Evaluation Study (REDS) to identify associations with donor age, sex, and ancestry-specific genetic polymorphisms in regions encoding *PFKP*, *HK1*, and *CD38*/*BST1*. Findings were validated in fresh and stored RBCs from 525 Diversity Outbred mice and through multi-omics profiling of 1,929 samples from 643 human RBC storage units. Associations between RBC ATP and hypoxanthine levels (and their linked genetic traits) and hemolysis were examined in vitro and in vivo among healthy autologous recipients and 5,816 critically ill heterologous transfusion recipients.
What was found
Donor genetic variants in *PFKP*, *HK1*, and *CD38*/*BST1* were associated with end-of-storage glycolytic metabolite levels. ATP and hypoxanthine levels, together with their underlying genetic traits, were associated with in vitro hemolysis as well as in vivo hemolysis in both healthy autologous transfusion recipients and critically ill patients. The abstract reported no specific numerical values, effect sizes, or p-values.
Why it matters
This study links donor genetic variations controlling RBC energy status during storage directly to transfusion-induced hemolysis, highlighting potential biological markers to optimize donor selection and improve transfusion outcomes.
Limits
The abstract does not provide numerical effect sizes, relative risks, or confidence intervals. The human clinical components are observational cohorts subject to residual confounding, and the abstract does not report whether genotype-guided donor unit matching prospectively improves clinical endpoints.
Cited by
- supports Red blood cells lack mitochondria and must use glucose for their metabolism.