红细胞的药物基因组学：研究药物转运蛋白基因变异体的模型。
Pharmacogenomics with red cells: a model to study protein variants of drug transporter genes.
机构信息
Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Clinical Pharmacology Program, Office of the Clinical Director, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
出版信息
Vox Sang. 2021 Feb;116(2):141-154. doi: 10.1111/vox.12999. Epub 2020 Sep 30.
The PharmacoScan pharmacogenomics platform screens for variation in genes that affect drug absorption, distribution, metabolism, elimination, immune adverse reactions and targets. Among the 1,191 genes tested on the platform, 12 genes are expressed in the red cell membrane: ABCC1, ABCC4, ABCC5, ABCG2, CFTR, SLC16A1, SLC19A1, SLC29A1, ATP7A, CYP4F3, EPHX1 and FLOT1. These genes represent 5 ATP-binding cassette proteins, 3 solute carrier proteins, 1 ATP transport protein and 3 genes associated with drug metabolism and adverse drug reactions. Only ABCG2 and SLC29A1 encode blood group systems, JR and AUG, respectively. We propose red cells as an ex vivo model system to study the effect of heritable variants in genes encoding the transport proteins on the pharmacokinetics of drugs. Altered pharmacodynamics in red cells could also cause adverse reactions, such as haemolysis, hitherto unexplained by other mechanisms.
PharmacoScan 药物基因组学平台可筛查影响药物吸收、分布、代谢、消除、免疫不良反应和靶点的基因变异。在该平台检测的 1191 个基因中，有 12 个基因在红细胞膜中表达：ABCC1、ABCC4、ABCC5、ABCG2、CFTR、SLC16A1、SLC19A1、SLC29A1、ATP7A、CYP4F3、EPHX1 和 FLOT1。这些基因代表 5 种 ABC 结合蛋白、3 种溶质载体蛋白、1 种 ATP 转运蛋白和 3 种与药物代谢和不良反应相关的基因。只有 ABCG2 和 SLC29A1 分别编码血型系统 JR 和 AUG。我们提出红细胞作为一种体外模型系统，用于研究编码转运蛋白的基因中遗传变异对药物药代动力学的影响。红细胞中药物动力学的改变也可能导致不良反应，如溶血，迄今为止尚未用其他机制解释。
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