Effect Of CYP3 A4?CYP3 A5?ABCB1 Gene Polymorphism And Tacrolimus Concentration On The Clinical Efficacy Of Patients With Nephrotic Syndrome In Chinese Population

PurposeTacrolimus is a novel potent immunosuppressive agent to treat nephrotic syndrome.The efficacy of tacrolimus is variable,which might be related to genetic variation and the blood concentration of tacrolimus?C₀?among patients.Previous studies focused on the impact of gene polymorphism on C₀ in renal transplant recipients,but little is known in patients with nephrotic syndrome.Therefore,we aim to investigate the effects of CYP3A4*1G,CYP3 A5*3,ABCB1?C1236T,G2677T/A?gene polymorphism and C₀ on the clinical efficacy of patients with nephrotic syndrome.MethodsA total of 100 nephrotic syndrome patients with a mean age of 37.28±17.0 years between January and December 2016 were included in this study.Glomerular filtration rate was greater than 80 ml/min/1.73m2 in all patients.All patients were treated with steroids plus TAC.Prednisone was used 1 mg/kg daily initially.After 8 weeks of treatment,the amount of prednisone was reduced by 5 mg every two weeks to 20 mg.Then,the dose of 20 mg/d was maintained for 2 months and the rest of the prednisone gradually reduced to complete withdrawal.TAC was given at the dose of 0.05 mg/kg/day for all patients,divided twice from oral application at intervals of 12 hours.On the sixth morning?after taking the medicine 10 times?,venous blood was collected to detect the blood concentration of TAC before drug administration.In this study,enzyme immunoassay enhancement?EMIT?was used to measure C₀,and Sanger sequencing was used to detect the genotypes of CYP3 A4*1G,CYP3 A5*3,ABCB1 1236C>T and ABCB1 2677G>T/A in 100 patients with nephrotic syndrome who were treated with tacrolimus.Then,we analyzed the effect of gene polymorphism and C₀ on the clinical efficacy of patients with nephrotic syndrome.Results1 In this study,we collected 100 patients who were treated with tacrolimus.Results showed that the distribution of the gene polymorphism in CYP3 A4*1G,CYP3 A5*3,ABCB1 C1236T and ABCB1 G2677T/A were in accordance with Hardy-Weinberg genetic equilibrium?P>0.05?,and the selected samples had group representation.2 The mutant allele frequencies of CYP3A4*1G,CYP3A5*3,ABCB1 C1236T and ABCB1 G2677T/A were 23%,74%,68%and 58.5%,respectively.The result of multi factor logistic regression analysis showed that the factors that influence the clinical therapeutic effects are ABCB1 1236 mutation genotype TT?P=0.01,OR=12.83?,ABCB1G2677T/A mutation genotype TT or TA or AA?P=0.034,OR=6.50?and Body mass index BMI?P=0.01,OR=17.06?.For ABCB1 C1236T,TT genotype can increase the effectiveness of clinical treatment 12.83 times compared with CC and CT genotype.As for ABCB1 G2677T/A,the clinical efficacy of patients with mutant genotype was 6.50 times than that of wild-type and heterozygous patients.Overweight patients can improve the clinical efficacy by 17.06 times than that of whose BMI is in normal range.3 We haven't found that CYP3 A4,CYP3 A5 and whether the use of the CCB class antihypertensive drugs have impacts on the clinical treatment of patients with nephrotic syndrome.4 The blood concentration of tacrolimus?C₀?can affect the clinical efficacy.And the clinical efficacy rate of patients with standard C₀ is higher than those substandard.Conclusions1 ABCB1 C1236T,ABCB1 G2677T/A genotype and body mass index?BMI?are the factors influencing the clinical efficacy of nephrotic syndrome.2 Detecting the related genes is helpful to optimize the drug administration program and improve the curative effect and it should be encouraged in clinical work.3 The blood drug level is closely related to the clinical efficacy and the clinical treatment effect on patients with standard C₀ is good.