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Association between CES1 rs2244613 and the pharmacokinetics and safety of dabigatran: Meta-analysis and quantitative trait loci analysis

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单位： [1]Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China. [2]National Center for Respiratory Medicine, Beijing, China. [3]Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China. [4]National Clinical Research Center for Respiratory Diseases, Beijing, China. [5]Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. [6]Shenzhen WeGene Clinical Laboratory, Shenzhen, China. [7]WeGene, Shenzhen Zaozhidao Technology Co., Ltd., Shenzhen, China. [8]Hunan Provincial Key Lab on Bioinformatics, School of Computer Science and Engineering, Central South University, Changsha, China. [9]Graduate School of Capital Medical University, Beijing, China. [10]Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria, Universidad Autónoma de Madrid, Madrid, Spain. [11]Department of Clinical Research and Data Management, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China. [12]Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. [13]VTT Technical Research Centre of Finland Ltd., Espoo, Finland. [14]Department of Dermatology, China-Japan Friendship Hospital, Beijing, China. [15]Department of Pharmacy, China-Japan Friendship Hospital, Beijing, China.

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To date, the influence of the carboxylesterase 1 (CES1) rs2244613 genotype on the pharmacokinetics (PKs) and safety of dabigatran remains controversial. Hence, a systematic review was performed to study the association between CES1 rs2244613 genotype and the PKs and safety of dabigatran and CES1 relative expression.In addition to the three English databases (Web of Science, PubMed, and Embase), two Chinese databases (CNKI and Wanfang) were thoroughly revised. The mean differences (MD) and corresponding 95% confidence intervals (CI) were applied to evaluate the differences in PKs between the CES1 rs2244613 genotype. Odds ratio (OR) was used to study the risk for bleeding events between the CES1 rs2244613 genotypes. Subsequent expression quantitative trait loci (eQTL) analyses were performed to evaluate genotype-specific expressions in human tissues.Ten studies (n = 2,777) were included. CES1 rs2244613 G allele carriers exhibited significantly lower dabigatran trough concentrations compared to T allele carriers (MD: -8.00 ng/mL; 95% CI: -15.08 to -0.92; p = 0.03). The risk for bleeding events was significantly lower in carriers of the G allele compared to T allele carriers (OR: 0.65; 95% CI: 0.44-0.96; p = 0.03). Subsequent eQTL analysis showed significant genome-wide expressions in two human tissues, whole blood (p = 5.1 × 10-10) and liver (p = 6.2 × 10-43).Our meta-analysis indicated a definite relation between the CES1 rs2244613 genotype and tolerability variations or pharmacokinetic fluctuations. The carriers of T allele showed higher dabigatran concentrations; therefore, they would benefit from a dose reduction.[https://inplasy.com/inplasy-2022-6-0027/], identifier [NPLASY202260027].Copyright © 2022 Li, Zhang, Weng, Qiu, Zubiaur, Zhang, Fan, Yang, Vuorinen, Zuo, Zhai and Wang.

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出版当年[2021]版：

大类 | 3 区医学

小类 | 3 区心脏和心血管系统

最新[2025]版：

大类 | 3 区医学

小类 | 3 区心脏和心血管系统

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出版当年[2020]版：

Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

最新[2023]版：

Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

影响因子： 最新[2023版] 2.8 最新五年平均[2021-2025] 3.1 出版当年[2020版] 6.05 出版当年五年平均[2016-2020] 0 出版前一年[2019版] 3.915 出版后一年[2021版] 5.848

第一作者：

第一作者单位： [1]Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China. [2]National Center for Respiratory Medicine, Beijing, China. [3]Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China. [4]National Clinical Research Center for Respiratory Diseases, Beijing, China. [5]Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

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通讯作者：

通讯机构： [1]Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China. [2]National Center for Respiratory Medicine, Beijing, China. [3]Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China. [4]National Clinical Research Center for Respiratory Diseases, Beijing, China. [14]Department of Dermatology, China-Japan Friendship Hospital, Beijing, China. [15]Department of Pharmacy, China-Japan Friendship Hospital, Beijing, China.

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