College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310000, China.
Nucleic Acids Res. 2020 Jan 8;48(D1):D1042-D1050. doi: 10.1093/nar/gkz779.
The absorption, distribution and excretion of drugs are largely determined by their transporters (DTs), the variability of which has thus attracted considerable attention. There are three aspects of variability: epigenetic regulation and genetic polymorphism, species/tissue/disease-specific DT abundances, and exogenous factors modulating DT activity. The variability data of each aspect are essential for clinical study, and a collective consideration among multiple aspects becomes crucial in precision medicine. However, no database is constructed to provide the comprehensive data of all aspects of DT variability. Herein, the Variability of Drug Transporter Database (VARIDT) was introduced to provide such data. First, 177 and 146 DTs were confirmed, for the first time, by the transporting drugs approved and in clinical/preclinical, respectively. Second, for the confirmed DTs, VARIDT comprehensively collected all aspects of their variability (23 947 DNA methylations, 7317 noncoding RNA/histone regulations, 1278 genetic polymorphisms, differential abundance profiles of 257 DTs in 21 781 patients/healthy individuals, expression of 245 DTs in 67 tissues of human/model organism, 1225 exogenous factors altering the activity of 148 DTs), which allowed mutual connection between any aspects. Due to huge amount of accumulated data, VARIDT made it possible to generalize characteristics to reveal disease etiology and optimize clinical treatment, and is freely accessible at: https://db.idrblab.org/varidt/ and http://varidt.idrblab.net/.
药物的吸收、分布和排泄在很大程度上取决于其转运体（DTs），因此其变异性引起了相当大的关注。变异性有三个方面：表观遗传调控和遗传多态性、物种/组织/疾病特异性 DT 丰度，以及调节 DT 活性的外源性因素。每个方面的变异性数据对于临床研究都是必不可少的，而在精准医学中，多方面的综合考虑至关重要。然而，目前没有数据库提供 DT 变异性所有方面的综合数据。在此，引入了药物转运体变异性数据库（VARIDT）来提供这些数据。首先，通过批准和临床/临床前的转运药物，首次确定了 177 种和 146 种 DT。其次，对于已确定的 DT，VARIDT 全面收集了其变异性的所有方面（23947 个 DNA 甲基化、7317 个非编码 RNA/组蛋白调控、1278 个遗传多态性、257 个 DT 在 21781 名患者/健康个体中的差异丰度谱、245 个 DT 在人类/模式生物 67 种组织中的表达、1225 个改变 148 个 DT 活性的外源性因素），这使得任何方面都可以相互连接。由于积累了大量的数据，VARIDT 使得概括特征成为可能，以揭示疾病病因并优化临床治疗，可在以下网址免费获取：https://db.idrblab.org/varidt/ 和 http://varidt.idrblab.net/。
