Pharmacogenomics and Personalized Medicine (Apr 2020)
Effects of CYP3A5 Polymorphisms on Efficacy and Safety of Tacrolimus Therapy in Patients with Idiopathic Membranous Nephropathy
Abstract
Chengning Zhang,1,* Suyan Duan,1,* Miao Guo,2 Yanggang Yuan,1 Zhimin Huang,1 Jingfeng Zhu,1 Bin Sun,1 Bo Zhang,1 Changying Xing1 1Departments of Nephrology; 2Department of Pharmacy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changying XingDepartment of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, 300 Guangzhou Road, Nanjing 210029, Jiangsu Province, People’s Republic of ChinaTel/Fax +86-25-6830-6462Email [email protected]: Tacrolimus (TAC) is beneficial for patients with idiopathic membranous nephropathy (IMN). It has a narrow therapeutic concentration range and many factors influence TAC blood concentration. CYP3A5 is the most important enzyme in TAC metabolism. The aim of this study was to analyze the effects of CYP3A5 gene polymorphisms on the efficacy and safety of TAC in IMN patients.Patients and Methods: Patients with IMN who received oral TAC (0.05– 0.075mg/kg/day) combined with prednisone (0.5mg/kg/day) from March 2016 to October 2018 were included. The data of clinical characteristics, therapeutic drugs and adverse reactions of patients were collected at baseline and during 24 weeks of treatment. Patients were divided into two groups according to different CYP3A5 genetic polymorphisms. The significant differences in the efficacy and side effects between the two groups were analyzed.Results: A total of 76 patients who completed follow-up were divided into CYP3A5 nonexpresser (CYP3A5*3/*3) group and CYP3A5 expresser (CYP3A5 *1/*3) group. The significant association between the CYP3A5 phenotype and TAC metabolism was observed. A total of 43 case-times patients exhibited adverse effects. The infection rate in CYP3A5 nonexpresser group (21.95%) was remarkably higher than the rate in CYP3A5 expresser group (5.71%). Blood concentration and C0/D levels were risk factors for adverse events through logistic regression analysis. There was no statistical difference between the study groups with respect to the efficacy.Conclusion: Our results demonstrated that CYP3A5 polymorphisms had important guiding roles in the treatment of IMN with tacrolimus. CYP3A5 expressers required higher daily doses of TAC to achieve the target drug concentration, but with fewer side effects. CYP3A5 genetic polymorphism might be used for TAC dosing adjustment to optimize the treatment for patients with IMN.Keywords: CYP3A5 polymorphisms, idiopathic membranous nephropathy, tacrolimus, side effects
