Study On The Influence Of ABCB1 G2677T Gene Polymorphism On Membranous Nephropathy Patients Treated With Tacrolimus

BackgroundMembranous nephropathy?MN?is one of the pathological types that cause nephrotic syndrome,and its incidence has increased in recent years.Tacrolimus is the most commonly used drug for MN clinical treatment,with advantages such as less adverse reactions and better patient compliance.However,the effective blood concentration range of tacrolimus is narrow,and the blood concentration and clinical efficacy of different individuals under the same dosing regimen are significantly different.Therefore,it is of positive significance to study influence factors of blood concentration and clinical efficacy of tacrolimus for disease treatment.P-glycoprotein encoded by ABCB1 G2677T gene is distributed on the surface of intestinal mucosa and has the effect of pumping tacrolimus from outside the intestinal cavity back into the intestinal cavity.ABCB1 G2677T gene polymorphism has a great influence on the function and activity of P-glycoprotein.Studies about whether it will further affect the blood concentration and clinical efficacy of tacrolimus in MN patients are currently rare.ObjectiveTo explore the influence of ABCB1 G2677T gene polymorphism on blood concentration and clinical efficacy after tacrolimus treatment in MN patients,and to provide evidence-based medical evidence for individualized drug treatment of MN patients.Methods116 MN patients who were hospitalized or outpatients in the Nephrology Department of Xuchang Central Hospital from January 2017 to March 2019 were prospectively included.All patients were diagnosed by renal biopsy pathological analysis.Fluorescence staining in situ hybridization was used to detect ABCB1 G2677T gene polymorphism in patients.On the basis of test results,patients were divided into three groups:A,B and C.ACB1 G2677T gene type was GG in Group A,GT in Group B and TT in Group C.The blood concentration of tacrolimus was determined by homogeneous enzyme immunoassay?HEI?.Differences between three groups for the first monitoring of minimum tacrolimus blood concentration control rate were compared,differences between three groups of tacrolimus blood concentration and daily dose during treatment were analyzed,changes in24-hour urine protein amount and serum albumin level between three groups before and after treatment were observed,differences between three groups in treatment efficiency and incidence of adverse drug reactions were compared,as well as differences in minimum tacrolimus blood concentration between different treatment effects.Reference range of minimum tacrolimus blood concentration in MN treatment was 5-10 ng/mL,the dosage regimen was adjusted in this study on the basis of monitoring results of minimum tacrolimus blood concentration.All patients took 30 days as a course of treatment,6consecutive courses of treatment,and were followed up in the first month,third month,and sixth month after treatment.SPSS 24.0 software was used for statistical analysis of study data.The measurement data were analyzed by one-way analysis of variance,kruskal-Wallis test and repeated measurement data analysis of variance.The comparison of count data was conducted by chi-square test,and the significance level a was 0.05.Results1 3 patients in Group A,5 patients in Group B and 1 patient in Group C were expulsed.A total of 107 patients completed the study.There was no statistically significant difference in expulsion rate between three groups??²=0.877,P=0.645?,no statistical difference between the measured value and theoretical value of each detected type of ABCB1 G2677T gene??²=0.682,P=0.711?,which was consistent with Hardy-Weinberg genetic balance.2 Minimum tacrolimus blood concentration control rates for the first monitoring in three groups were significantly different,the control rate in Group A was higher than that in Group B,and the difference was statistically significant?P<0.05?;minimum tacrolimus blood concentration in three groups?C₀?,minimum tacrolimus blood concentration and daily dose ratio?C₀/D?were significantly different,C₀ in Group A was compared with those in Groups B and C and C₀/D in Group A was compared with that in Group C,and the differences were statistically significant?P<0.05?.3 24-hour urine protein volume of three groups had a tendency to change with the treatment time?F=824.41,P<0.05?,24-hour urine protein volume of each group after treatment was lower than before treatment;ABCB1 G2677T gene types?GG,GT,TT?had an interaction with the treatment time?F=5.327,P=0.018?,24-hour urine protein volume of three groups varied with time.4 Serum albumin levels of three groups had a tendency to change with the treatment time?F=771.43,P<0.05?,the amount of serum albumin after treatment in each group was higher than before treatment;ABCB1 G2677T gene types?GG,GT,TT?had no interaction with the treatment time?F=1.544,P=0.081?,the amount of serum albumin in three groups had the same trend with time.ABCB1 G2677T gene types?GG,GT,TT?had no effect on changes in serum albumin levels in MN patients treated with tacrolimus.5 The effective rate of treatment in Group A was 73.53%,higher than 70.21%in Group B and 65.38%in Group C,the difference was not statistically significant??²=0.467,P=0.792?.6 The minimum tacrolimus blood concentration of patients with complete remission was?6.62±2.17?ng/mL,higher than?5.47±1.31?ng/mL of patients with partial remission and?4.32±0.87?ng/mL of patients with ineffective treatment,minimum tacrolimus blood concentration between different treatment effects was pairwise compared,and the difference was statistically significant?P<0.05?.7 Incidence of abnormal liver function enzymology and total incidence of adverse drug reactions in three groups were significantly different,and the difference in total incidence of adverse drug reactions between Group A and Group C was statistically significant?P<0.05?.ConclusionABCB1 G2677T gene polymorphism has an influence on the blood concentration of MN patients treated with tacrolimus.Among them,GG patients'minimum blood concentration can reach the standard quickly;ABCB1 G2677T gene polymorphism influences the occurrence of tacrolimus adverse reactions,and incidence of adverse drug reactions of GG patients is higher than that of GT and TT patients.