Influence of multidrug resistant gene polymorphisms and haplotype on blood con-centration of tacrolimus in individuals in stable phases after renal transplantation / 药学实践杂志

ABSTRACT

Objective To study the relevance between the polymorphisms and haplotype of multidrug resistant gene (MDR1) and the ratio of blood concentration/dosage in individuals treated by tacrolimus in stable phases post renal transplanta-tion ,and to provide data for personalized FK-506 administration .Methods The MDR1 C1236T ,G2677T/A and C3435T gen-otypes of 104 renal transplantation patients were determined by PCR followed sequencing method .The blood concentration of tacrolimus was detected by EMIT method .The differences in concentration/(dose × weight) (C/D) ratios were compared a-mong all of the genotype groups treated by tacrolimus .Results In the 104 renal transplantation recipients ,the frequency of MDR1 C1236T ,G2677T/A and C3435T mutation alleles was 56 .73% ,55 .77% and 33 .17% ,respectively .A correlation was revealed among SNP of MDR1 C3435T ,TTT haplotype and the C/D ratios (P<0.05) .In patients of CYP3A5*3*3 ,A cor-relation was also found among TTT haplotype and the C/D ratios (P< 0.05) .No difference was found among the MDR1 C1236T ,G2677T/A ,CGC haplotype and the C/D ratios (P>0.05) .Conclusion It is demonstrated that genetic polymor-phisms of MDR1 C3435T and TTT haplotype are correlated with C/D ratio of tacrolimus in Chinese renal transplant patients in stable stage .These findings affect the dose-adjusted concentration of tacrolimus individually .