title: The heritability of hemolysis in stored human red blood cells.
abstract: BACKGROUND
  The transfusion of red blood cells (RBCs) with maximum therapeutic efficacy is a major goal in transfusion medicine. One of the criteria used in determining stored RBC quality is end-of-storage hemolysis. Between donors, a wide range of hemolysis is observed under identical storage conditions. Here, a potential mechanism for this wide range is investigated. We hypothesize that the magnitude of hemolysis is a heritable trait. Also, we investigated correlations between hemolysis and RBC metabolites; this will establish pathways influencing hemolysis as future targets for genetic analysis.
  
  
  METHODS
  Units of RBCs from identical and nonidentical twins were collected and stored under standard conditions for 56 days. Hemolysis, adenosine triphosphate (ATP), and total glutathione (tGSH) were measured throughout storage. Nontargeted metabolic analyses were performed on RBCs that had been stored for 28 days. Heritability was determined by comparing values between identical and nonidentical twins.
  
  
  RESULTS
  Hemolysis was found to be heritable (mean > 45%) throughout the storage period. Potential correlations were observed between hemolysis and metabolites from the purine metabolism, lysolipid, and glycolysis pathways. These also exhibited heritability (>20%). No correlation was found with ATP or tGSH.
  
  
  CONCLUSIONS
  The susceptibility of RBCs to lysis during storage is partly determined by inheritance. We have also uncovered several pathways that are candidate targets for future genomewide association studies. These findings will aid in the design of better storage solutions and the development of donor screening tools that minimize hemolysis during storage.
authors: Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, Iowa.
authors: Thomas J
authors: TJ
authors: Van 't Erve
authors: Free Radical and Radiation Biology Program, Radiation Oncology, University of Iowa, Iowa City, Iowa.
authors: Brett A
authors: BA
authors: Wagner
authors: Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors: Sean M
authors: SM
authors: Martin
authors: Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors: C Michael
authors: CM
authors: Knudson
authors: Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors: Robyn
authors: R
authors: Blendowski
authors: Metabolon, Inc., Durham, North Carolina.
authors: Mignon
authors: M
authors: Keaton
authors: Metabolon, Inc., Durham, North Carolina.
authors: Tracy
authors: T
authors: Holt
authors: Department of Laboratory Medicine, University of Washington, Seattle, Washington.
authors: John R
authors: JR
authors: Hess
authors: Free Radical and Radiation Biology Program, Radiation Oncology, University of Iowa, Iowa City, Iowa.|Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa.
authors: Garry R
authors: GR
authors: Buettner
authors: Department of Epidemiology, College of Public Health, University of Iowa.
authors: Kelli K
authors: KK
authors: Ryckman
authors: Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors: Benjamin W
authors: BW
authors: Darbro
authors: Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors: Jeffrey C
authors: JC
authors: Murray
authors: Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors: Thomas J
authors: TJ
authors: Raife
mesh_terms: D000328:Adult; D001782:Blood Donors; D001793:Blood Preservation; D001827:Body Height / Q000235:genetics; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics; D004909:Erythrocyte Indices; D004912:Erythrocytes / Q000737:chemistry / Q000502:physiology*; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006461:Hemolysis / Q000235:genetics*; D006801:Humans; D047589:Leukocyte Reduction Procedures; D008297:Male; D055442:Metabolome / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D013997:Time Factors; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic; D055815:Young Adult
chemical_list: D006454:Hemoglobins
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