Effect of CYP3A5 genetic polymorphism on tacrolimus concentration in myasthenia gravis patients
10.3760/cma.j.issn.1671-8925.2018.01.009
- VernacularTitle:CYP3A5基因多态性对重症肌无力患者他克莫司血药浓度的影响
- Author:
Di CHEN
1
;
Shifang HOU
;
Ming ZHAO
;
Xuelin SUN
;
Hua ZHANG
;
Liping YANG
Author Information
1. 100730 北京,北京医院国家老年医学中心,药学部药物临床风险与个体化应用评价北京市重点实验室
- Keywords:
Myasthenia gravis;
Tacrolimus;
CYP3A5;
Polymorphism;
Plasma concentration
- From:
Chinese Journal of Neuromedicine
2018;17(1):48-52
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of CYP3A5 genetic polymorphism on tacrolimus concentration in myasthenia gravis patients to explore the optimum doses for patients of different genotypes.Methods The CYP3A 5 genotypes of 95 myasthenia gravis patients treated with tacrolimus in our hospital from January 2013 to December 2015,were determined by fluorescence in situ hybridization and tacrolimus concentrations were determined by chemiluminescence microparticle immuno assay.The differences of tacrolimus concentrations/dosage (C/D) ratios,concentration and dosage oftacrolimus were compared among patients of different genotypes.Results There were 14 patients (14.74％) with CYP3A5*l*l,35 (36.84％) with CYP3A5*l*3 and46 (48.42％) with CYP3A5*3*3 in these 95 patients.The allele frequencies of *1 and *3 were 33.16％ and 66.84％,respectively.The C/D ratios of patients from the 3 groups were significantly different (F=24.860,P=0.000):the C/D ratio of CYP3A5*1/*1 patients was significantly lower than that of CYP3A5*1/*3 patients (P＜0.05),and that of CYP3A5*1/*3 carriers was significantly lower than that of CYP3A5*3/*3 patients (P＜0.05).The appropriate doses of tacrolimus of myasthenia gravis patients were different in different genotypes patients:the dose of patients with CYP3A5* 1* 1 was 4-5 mg/d,that of CYP3A5*3*3 was 2-3 mg/d,and that of CYP3A5*1*3 was between that of CYP3A5*1*1 and CYP3A5*3*3.Conclusions The polymorphism of CYP3A 5 genetic polymorphism has effect on plasma concentrations oftacrolimus in patients with myasthenia gravis.Clinical application ofpharmacogenetic studies will be helpful for individualization oftacrolimus appropriate dosage.
