Title: Effect of CYP3A5 genetic polymorphism on tacrolimus concentration in myasthenia gravis patients
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 CYP3A5 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 of tacrolimus were compared among patients of different genotypes.
Results
There were 14 patients (14.74%) with CYP3A5*1*1, 35 (36.84%) with CYP3A5*1*3 and 46 (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 CYP3A5 genetic polymorphism has effect on plasma concentrations of tacrolimus in patients with myasthenia gravis. Clinical application of pharmacogenetic studies will be helpful for individualization of tacrolimus appropriate dosage.
Key words:
Myasthenia gravis; Tacrolimus; CYP3A5; Polymorphism; Plasma concentration
Publication Year: 2018
Publication Date: 2018-01-15
Language: en
Type: article
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