Journal article
Functional effects of an African glucose-6-phosphate dehydrogenase (G6PD) polymorphism (Val68Met) on red blood cell hemolytic propensity and post-transfusion recovery
Transfusion (Philadelphia, Pa.), Vol.64(4), pp.615-626
04/2024
DOI: 10.1111/trf.17756
PMCID: PMC11003845
PMID: 38400625
Appears in UI Libraries Support Open Access
Abstract
Donor genetic variation is associated with red blood cell (RBC) storage integrity and post-transfusion recovery. Our previous large-scale genome-wide association study demonstrated that the African G6PD deficient A- variant (rs1050828, Val68Met) is associated with higher oxidative hemolysis after cold storage. Despite a high prevalence of X-linked G6PD mutation in African American population (>10%), blood donors are not routinely screened for G6PD status and its importance in transfusion medicine is relatively understudied.
To further evaluate the functional effects of the G6PD A- mutation, we created a novel mouse model carrying this genetic variant using CRISPR-Cas9. We hypothesize that this humanized G6PD A- variant is associated with reduced G6PD activity with a consequent effect on RBC hemolytic propensity and post-transfusion recovery.
G6PD A- RBCs had reduced G6PD protein with ~5% residual enzymatic activity. Significantly increased in vitro hemolysis induced by oxidative stressors was observed in fresh and stored G6PD A- RBCs, along with a lower GSH:GSSG ratio. However, no differences were observed in storage hemolysis, osmotic fragility, mechanical fragility, reticulocytes, and post-transfusion recovery. Interestingly, a 14% reduction of 24-h survival following irradiation was observed in G6PD A- RBCs compared to WT RBCs. Metabolomic assessment of stored G6PD A- RBCs revealed an impaired pentose phosphate pathway (PPP) with increased glycolytic flux, decreasing cellular antioxidant capacity.
This novel mouse model of the common G6PD A- variant has impaired antioxidant capacity like humans and low G6PD activity may reduce survival of transfused RBCs when irradiation is performed.
Details
- Title: Subtitle
- Functional effects of an African glucose-6-phosphate dehydrogenase (G6PD) polymorphism (Val68Met) on red blood cell hemolytic propensity and post-transfusion recovery
- Creators
- Ling Wang - University of IowaElizabeth R Rochon - University of Maryland, BaltimoreSebastien Gingras - University of PittsburghBenjamin E Zuchelkowski - University of Pittsburgh Medical CenterDerek J Sinchar - University of Pittsburgh Medical CenterElimira Alipour - Wake Forest UniversityJulie A Reisz - University of Colorado Anschutz Medical CampusMinying Yang - University of Pittsburgh Medical CenterGrier P Page - RTI InternationalTamir Kanias - VitalantDarrell J Triulzi - University of PittsburghJanet S Lee - Washington University in St. Louis School of MedicineDaniel B Kim-Shapiro - Wake Forest UniversityAngelo D'Alessandro - University of Colorado Anschutz Medical CampusMark T Gladwin - University of Maryland, Baltimore
- Resource Type
- Journal article
- Publication Details
- Transfusion (Philadelphia, Pa.), Vol.64(4), pp.615-626
- DOI
- 10.1111/trf.17756
- PMID
- 38400625
- PMCID
- PMC11003845
- NLM abbreviation
- Transfusion
- eISSN
- 1537-2995
- Publisher
- Wiley
- Grant note
- National Institutes of Health (NIH). Grant Numbers: R01HL12886, R01AG073257, R21DE032197, R01HL098032, 5R01AR076357, 5R01HL098032, R01HL148151, R01HL149714, R01HL146442, UH3HL143192, 5P01HL103455, 2R01HL125886
- Language
- English
- Electronic publication date
- 02/23/2024
- Date published
- 04/2024
- Academic Unit
- Orthopedics and Rehabilitation
- Record Identifier
- 9984563557102771
Metrics
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