title: The heritability of metabolite concentrations in stored human red blood cells.
abstract: BACKGROUND
  The degeneration of red blood cells (RBCs) during storage is a major issue in transfusion medicine. Family studies in the 1960s established the heritability of the RBC storage lesion based on poststorage adenosine triphosphate (ATP) concentrations. However, this critical discovery has not been further explored. In a classic twin study we confirmed the heritability of poststorage ATP concentrations and established the heritability of many other RBC metabolites.
  
  
  METHODS
  ATP concentrations and metabolomic profiles were analyzed in RBC samples from 18 twin pairs. On samples stored for 28 days, the heritability of poststorage ATP concentrations were 64 and 53% in CP2D- and AS-3-stored RBCs, respectively.
  
  
  RESULTS
  Metabolomic analyses identified 87 metabolites with an estimated heritability of 20% or greater. Thirty-six metabolites were significantly correlated with ATP concentrations (p ≤ 0.05) and 16 correlated with borderline significance (0.05 ≤ p ≤ 0.10). Of the 52 metabolites that correlated significantly with ATP, 24 demonstrated 20% or more heritability. Pathways represented by heritable metabolites included glycolysis, membrane remodeling, redox homeostasis, and synthetic and degradation pathways.
  
  
  CONCLUSIONS
  We conclude that many RBC metabolite concentrations are genetically influenced during storage. Future studies of key metabolic pathways and genetic modifiers of RBC storage could lead to major advances in RBC storage and transfusion therapy.
authors.affiliation: Interdisciplinary Program in Human Toxicology, The University of Iowa, Iowa City, Iowa.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: van 't Erve
authors.forename: Brett A
authors.initials: BA
authors.lastname: Wagner
authors.forename: Sean M
authors.initials: SM
authors.lastname: Martin
authors.forename: C Michael
authors.initials: CM
authors.lastname: Knudson
authors.forename: Robyn
authors.initials: R
authors.lastname: Blendowski
authors.forename: Mignon
authors.initials: M
authors.lastname: Keaton
authors.forename: Tracy
authors.initials: T
authors.lastname: Holt
authors.forename: John R
authors.initials: JR
authors.lastname: Hess
authors.forename: Garry R
authors.initials: GR
authors.lastname: Buettner
authors.forename: Kelli K
authors.initials: KK
authors.lastname: Ryckman
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Darbro
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Murray
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Raife
mesh_terms: D000225:Adenine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000097:blood*; D000328:Adult; D001793:Blood Preservation; D015992:Body Mass Index; D002951:Citrates / Q000494:pharmacology; D004912:Erythrocytes / Q000737:chemistry* / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006019:Glycolysis / Q000235:genetics; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D047589:Leukocyte Reduction Procedures; D008297:Male; D008660:Metabolism / Q000235:genetics; D055432:Metabolomics; D010084:Oxidation-Reduction; D010710:Phosphates / Q000494:pharmacology; D019655:Quantitative Trait, Heritable; D012965:Sodium Chloride / Q000494:pharmacology; D012996:Solutions / Q000494:pharmacology; D013997:Time Factors; D014430:Twins, Monozygotic; D055815:Young Adult
chemical_list: C058647:AS-3 preservative solution; D002951:Citrates; D010710:Phosphates; D012996:Solutions; D012965:Sodium Chloride; C007077:citrate phosphate dextrose; D000255:Adenosine Triphosphate; D005947:Glucose; D000225:Adenine