التفاصيل البيبلوغرافية
| العنوان: |
Functional effects of an African glucose‐6‐phosphate dehydrogenase (G6PD) polymorphism ( Val68Met) on red blood cell hemolytic propensity and post‐transfusion recovery |
| المؤلفون: |
Wang, Ling, Rochon, Elizabeth R., Gingras, Sebastien, Zuchelkowski, Benjamin E., Sinchar, Derek J., Alipour, Elimira, Reisz, Julie A., Yang, Minying, Page, Grier P., Kanias, Tamir, Triulzi, Darrell J., Lee, Janet S., Kim‐Shapiro, Daniel B., D'Alessandro, Angelo, Gladwin, Mark T. |
| المساهمون: |
National Institutes of Health |
| المصدر: |
Transfusion ; volume 64, issue 4, page 615-626 ; ISSN 0041-1132 1537-2995 |
| بيانات النشر: |
Wiley |
| سنة النشر: |
2024 |
| المجموعة: |
Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: |
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. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1111/trf.17756 |
| الإتاحة: |
https://doi.org/10.1111/trf.17756Test |
| حقوق: |
http://creativecommons.org/licenses/by-nc/4.0Test/ |
| رقم الانضمام: |
edsbas.977EB2D7 |
| قاعدة البيانات: |
BASE |
