The heritability of metabolite concentrations in stored human red blood cells

Thomas J van 't Erve; Brett A Wagner; Sean M Martin; C Michael Knudson; Robyn Blendowski; Mignon Keaton; Tracy Holt; John R Hess; Garry R Buettner; Kelli K Ryckman; Benjamin W Darbro; Jeffrey C Murray; Thomas J Raife

doi:10.1111/trf.12605

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The heritability of metabolite concentrations in stored human red blood cells

Journal article

Open access

Peer reviewed

The heritability of metabolite concentrations in stored human red blood cells

Thomas J van 't Erve, Brett A Wagner, Sean M Martin, C Michael Knudson, Robyn Blendowski, Mignon Keaton, Tracy Holt, John R Hess, Garry R Buettner, Kelli K Ryckman, …

Transfusion (Philadelphia, Pa.), Vol.54(8), pp.2055-2063

08/2014

DOI: 10.1111/trf.12605

PMCID: PMC4138246

PMID: 24601981

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Abstract

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. 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. 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. 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.

Metabolomics

Sodium Chloride - pharmacology

Blood Preservation

Humans

Male

Adenosine Triphosphate - blood

Erythrocytes - chemistry

Glycolysis - genetics

Young Adult

Leukocyte Reduction Procedures

Time Factors

Adult

Female

Phosphates - pharmacology

Metabolism - genetics

Body Mass Index

Oxidation-Reduction

Quantitative Trait, Heritable

Adenine - pharmacology

Glucose - pharmacology

Twins, Monozygotic

Erythrocytes - drug effects

Solutions - pharmacology

Citrates - pharmacology

Homeostasis - genetics

ISRP Project 1 2015-2020

Details

Title: Subtitle: The heritability of metabolite concentrations in stored human red blood cells
Creators: Thomas J van 't Erve - Interdisciplinary Program in Human Toxicology, The University of Iowa, Iowa City, Iowa
Brett A Wagner
Sean M Martin
C Michael Knudson
Robyn Blendowski
Mignon Keaton
Tracy Holt
John R Hess
Garry R Buettner
Kelli K Ryckman
Benjamin W Darbro
Jeffrey C Murray
Thomas J Raife
Resource Type: Journal article
Publication Details: Transfusion (Philadelphia, Pa.), Vol.54(8), pp.2055-2063
DOI: 10.1111/trf.12605
PMID: 24601981
PMCID: PMC4138246
NLM abbreviation: Transfusion
ISSN: 0041-1132
eISSN: 1537-2995
Publisher: United States
Grant note: P30 ES005605 / NIEHS NIH HHS R01 GM073929 / NIGMS NIH HHS P42 ES013661 / NIEHS NIH HHS 2UL1TR000442 / NCATS NIH HHS R01GM073929 / NIGMS NIH HHS P30 ES05605 / NIEHS NIH HHS P01 HL046925 / NHLBI NIH HHS UL1 TR000442 / NCATS NIH HHS P30 CA086862 / NCI NIH HHS R01 CA169046 / NCI NIH HHS
Language: English
Date published: 08/2014
Academic Unit: Pathology; Medical Genetics and Genomics; Pediatric Dentistry; Craniofacial Anomalies Research Center; Nursing; Anatomy and Cell Biology; International Programs; Stead Family Department of Pediatrics; Epidemiology; Radiation Oncology; Public Policy Center (Archive); Dental Research; Iowa Superfund Research Program
Record Identifier: 9983995123302771

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