Clinical Biochemistry Section, Department of Neurological, Biomedical and Movement Sciences, University of Verona, Verona, Italy.
General Medicine and Hypertension Unit, Department of Medicine, University of Verona, Verona, Italy.
Clin Pharmacol Ther. 2019 Jun;105(6):1477-1491. doi: 10.1002/cpt.1323. Epub 2019 Feb 17.
The cytochrome P450 (CYP)4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at the individual patients level to capture the possible effect of ethnicity, gene-gene interaction, or other drugs on the association and to verify if inclusion of CYP4F23 variant into dosing algorithms improves the prediction of mean coumarin dose. We asked the authors of our previous meta-analysis (30 articles) and of 38 new articles retrieved by a systematic review to send us individual patients' data. The final collection consists of 15,754 patients split into a derivation and validation cohort. The CYP4F23 polymorphism was consistently associated with an increase in mean coumarin dose (+9% (95% confidence interval (CI) 7-10%), with a higher effect in women, in patients taking acenocoumarol, and in white patients. The inclusion of the CYP4F2*3 in dosing algorithms slightly improved the prediction of stable coumarin dose. New pharmacogenetic equations potentially useful for clinical practice were derived.
细胞色素 P450（CYP）4F2 基因被认为会影响香豆素的平均剂量。本研究旨在对个体患者水平进行荟萃分析，以捕捉种族、基因-基因相互作用或其他药物对该关联的可能影响，并验证将 CYP4F23 变体纳入剂量算法是否能提高香豆素平均剂量的预测能力。我们要求我们之前荟萃分析的作者（30 篇文章）和通过系统综述检索到的 38 篇新文章的作者向我们发送个体患者的数据。最终收集到了 15754 名患者，分为推导和验证队列。CYP4F23 多态性与香豆素平均剂量的增加一致（+9%（95%置信区间 7-10%）），女性、服用醋硝香豆素的患者和白人患者的影响更大。将 CYP4F2*3 纳入剂量算法略微提高了稳定香豆素剂量的预测能力。推导出了一些可能对临床实践有用的新遗传药理学方程。
