Influence of CYP3A5 and MDR1 gene polymorphisms on clinical efficacy and infectious complications of patients with mem-branous nephropathy after tacrolimus treatment
Objective To analyze the effects of cytochrome P450 enzyme 3A5(CYP3A5)and multidrug resistance gene 1(MDR1)gene polymorphisms on clinical efficacy and infectious complications in patients with primary membranous nephropathy(PMN)after tacrolimus treatment.Methods Totally 75 patients with PMN admitted to the 7th People's Hospital of Zhengzhou were enrolled between October 2020 and October 2022.Polymerase chain reaction with restriction fragment length polymorphism(PCR-RFLP)method was used to detect the gene polymorphisms of CYP3A5*3,MDR1 C1236T,MDR1 G2677T and MDR1 C3435T,and the difference in C/D value(tacrolimus blood concen-tration/dose×body mass)of tacrolimus of different genotypes and the effects on clinical efficacy and occurrence of infectious complications in PMN patients were compared.Results The mutation frequencies of *3/*3 genotype and G allele in CYP3A5*3 were 54.67%and 75.33%,and the mutation frequency of CT genotype in MDR1 C1236T was 57.33%,and the mutation frequency of GT genotype in MDR1 G2677T was 49.33%,and the mutation frequency of CT genotype in MDR1 C3435T was as high as 57.33%.The C/D value of tacrolimus of AA+AG geno-type in CYP3A5*3 was lower than that of GG genotype(P<0.05),and the C/D value of tacrolimus of CC genotype in MDR1 C3435T was lower than that of CT+TT genotype(P<0.05).There were no statistically significant differences in the effects of tacrolimus dose used for different genotypes of CYP3A5*3,MDR1 C1236T/A,and MDR1 G2677T on the clinical outcome of patients with PMN(P>0.05).The remission rate of tacrolimus dose used in the CT+TT genotype in MDR1 C3435T was higher than that in the CC genotype(71.70%vs 45.45%,P<0.05).There were no statistical differences between tacrolimus doses used for different genotypes of CYP3A5 and MDR1 on the incidence of infectious com-plications in patients with PMN(P>0.05).Conclusion GG genotype of CYP3A5*3 and CT+TT genotype of MDR1 C3435T can increase the C/D value of tacrolimus,and patients with CT+TT genotype of MDR1 C3435 T have better clinical efficacy of tacrolimus.
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