{"doi":"10.1111/trf.17756","title":"Functional effects of an African glucose‐6‐phosphate dehydrogenase (G6PD) polymorphism (<scp>Val68Met</scp>) on <scp>red blood cell</scp> hemolytic propensity and post‐transfusion recovery","abstract":"BACKGROUND: 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. STUDY DESIGN AND METHODS: 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. RESULTS: 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. DISCUSSION: 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.","journal":"Transfusion","year":2024,"id":441965,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9577,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":642203,"name":"Elizabeth R. Rochon","orcid":"0000-0002-6255-9817","position":1,"is_corresponding":false},{"id":526579,"name":"Sébastien Gingras","orcid":"0000-0003-2607-8642","position":2,"is_corresponding":false},{"id":526578,"name":"Benjamin E. Zuchelkowski","orcid":"0000-0002-0747-292X","position":3,"is_corresponding":false},{"id":1255484,"name":"Derek J Sinchar","orcid":null,"position":4,"is_corresponding":false},{"id":1255485,"name":"Elimira Alipour","orcid":null,"position":5,"is_corresponding":false},{"id":110268,"name":"Julie A. Reisz","orcid":"0000-0002-7296-4963","position":6,"is_corresponding":false},{"id":527518,"name":"Minying Yang","orcid":null,"position":7,"is_corresponding":false},{"id":73865,"name":"Grier P. Page","orcid":"0000-0003-2582-3786","position":8,"is_corresponding":false},{"id":257584,"name":"Tamir Kanias","orcid":"0000-0001-6558-0913","position":9,"is_corresponding":false},{"id":448036,"name":"Darrell J. Triulzi","orcid":null,"position":10,"is_corresponding":false},{"id":281863,"name":"Janet Lee","orcid":"0000-0002-6812-6043","position":11,"is_corresponding":false},{"id":347800,"name":"Daniel B. Kim‐Shapiro","orcid":"0000-0003-4383-3101","position":12,"is_corresponding":false},{"id":28360,"name":"Angelo D’Alessandro","orcid":"0000-0002-2258-6490","position":13,"is_corresponding":false},{"id":24963,"name":"Mark T. Gladwin","orcid":"0000-0001-7267-9006","position":14,"is_corresponding":false},{"id":309334,"name":"Ling Wang","orcid":"0000-0003-4333-3158","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T02:01:11.152920Z","pmid":"38400625","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}