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首页> 外文期刊>Genetic testing and molecular biomarkers >Tacrolimus Starting Dose Prediction Based on Genetic Polymorphisms and Clinical Factors in Chinese Renal Transplant Recipients
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Tacrolimus Starting Dose Prediction Based on Genetic Polymorphisms and Clinical Factors in Chinese Renal Transplant Recipients

机译：他克莫司剂量开始预测的基础上基因多态性和临床因素中国肾移植受者

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Aims:Tacrolimus has extensive pharmacokinetic variability among patients and a narrow therapeutic window. The U.S. Clinical Pharmacogenetics Implementation Consortium recommends a starting dose for tacrolimus of 0.15-0.3 mg center dot kg(-1)center dot day(-1), which is much higher compared with 0.05-0.15 mg center dot kg(-1)center dot day(-1)used in Chinese. The purpose of this study was to investigate the influence of clinical factors and single nucleotide polymorphisms (SNPs) on tacrolimus concentrations in Chinese renal transplant recipients. Methods:This study enrolled 406 tacrolimus-treated patients. After renal transplantation, the first tacrolimus trough concentration and corresponding clinical information were collected from all patients. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used to genotype 15 SNPs. The relationship between the genetic and clinical factors and dose-adjusted tacrolimus trough concentration was examined. The tacrolimus starting dose was predicted using a classification and regression tree analysis. Results:Examination of the 15 SNPs and several clinical factors identified theCYP3A5genotype (p = 5.6 x 10(-11)) and hemoglobin (p = 8.4 x 10(-10)) as the most significant determinants of tacrolimus C-0/D. Accordingly, a concise tacrolimus recommendation dosage model, a classification scheme, and a regression tree were developed. Conclusion:A new classification and regression tree model was developed for establishing the starting dose of tacrolimus based on theCYP3A5genotype and hemoglobin values. This result may help clinicians prescribe an appropriate initial tacrolimus dose.ClinicalTrials.govID: 2020-KY-147.
机译：目的:他克莫司已经广泛的药代动力学变化在病人和狭窄的治疗窗口。药物基因学实现财团建议的起始剂量他克莫司0.15 - -0.3毫克中心导公斤(1)中心导天(1)更高的比0.05 - -0.15毫克是什么中心圆点公斤(1)中心(1)用于点的一天中国人调查临床因素的影响单核苷酸多态性(SNPs)他克莫司浓度在中国肾移植受者。招收了406名tacrolimus-treated病人。肾移植,第一他克莫司槽浓度和相应的临床从所有病人信息收集。Matrix-assisted激光解吸/电离飞行时间质谱用于15单核苷酸多态性基因型。遗传和临床因素和dose-adjusted他克莫司谷浓度检查。他克莫司剂量开始使用预测分类和回归树分析。结果:考试的15个snp和几个临床因素确定theCYP3A5genotype (p= 5.6 x 10(-11))和血红蛋白(p = 8.4 x10(-10))的最重要的决定因素他克莫司C-0 / D。他克莫司推荐剂量模型中,分类方案,和回归树发展。回归树模型开发建立的起始剂量他克莫司基于theCYP3A5genotype和血红蛋白值。这一结果可以帮助临床医生开一个适当的初始他克莫司

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