van 't Erve Thomas J, Wagner Brett A, Martin Sean M, Knudson C Michael, Blendowski Robyn, Keaton Mignon, Holt Tracy, Hess John R, Buettner Garry R, Ryckman Kelli K, Darbro Benjamin W, Murray Jeffrey C, Raife Thomas J
Interdisciplinary Program in Human Toxicology, The University of Iowa, Iowa City, Iowa.
Transfusion. 2014 Aug;54(8):2055-63. doi: 10.1111/trf.12605. Epub 2014 Mar 6.
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.
红细胞（RBC）在储存过程中的退化是输血医学中的一个主要问题。20世纪60年代的家族研究基于储存后三磷酸腺苷（ATP）浓度确定了RBC储存损伤的遗传性。然而，这一关键发现尚未得到进一步探索。在一项经典的双胞胎研究中，我们证实了储存后ATP浓度的遗传性，并确定了许多其他RBC代谢物的遗传性。
分析了18对双胞胎的RBC样本中的ATP浓度和代谢组学谱。在储存28天的样本中，CP2D和AS-3储存的RBC中储存后ATP浓度的遗传性分别为64%和53%。
代谢组学分析确定了87种代谢物，估计遗传性为20%或更高。36种代谢物与ATP浓度显著相关（p≤0.05），16种代谢物与临界显著性相关（0.05≤p≤0.10）。在与ATP显著相关的52种代谢物中，24种表现出20%或更高的遗传性。可遗传代谢物代表的途径包括糖酵解、膜重塑、氧化还原稳态以及合成和降解途径。
我们得出结论，许多RBC代谢物浓度在储存过程中受到遗传影响。未来对RBC储存的关键代谢途径和遗传修饰因子的研究可能会在RBC储存和输血治疗方面取得重大进展。
