Multidrug resistance 1 gene polymorphism affects early mycophenolate mofetil exposure in Chinese renal transplant recipients / 中华器官移植杂志

ABSTRACT

Objective To investigate the relationship between the polymorphism of human multidrug resistance 1 gene(MDR1)polymorphism and early MMF pharmacokinetics.Methods Twenty-eight Chinese primary renal transplant recipients were emrolled.On day 14 post-transplant,patients took the MMF orally on fast.Whole blood samples(2 ml)were obtained at the following time pointspredose(G0)and 0.5,1,1.5,2,4,6,8,10 and 12 h(C0.5,C1,C1.5,G2,C4,C6,C8,C10,C12,respectively)postdose during the dosing interval.The MPA plasrna concentration was assayed by high performance liquid chromatography (HPLC).Pharmacokinetie parameters were determined by WINNOLIN 3.1.Three major single nucleotide polymorphisrrls(SNP),C1236 T,G2677 T/A,C3435 T of MDR1 were analyzed by PCR-RFLP.Pharmacokinetie parameters of MPA were compared between different MDR1 genotype and haplotype groups.Ailele frenqueneis were also compared in high(MPA area under concentratation-time curve 0～12 h,frequencies of 1236 TT,2677 TT/AA,3435 TT in three major MDR1 SNP positions,exons 12,21 and 26,were 0.368,0.184 and 0.211,respectively.MPA AUC was significantly higher in 1236 TT group than in 1236 CC/CT group(65.36±11.51 vs 53.33±13.77,P=0.032).On C1236 T SNP,TT genotype frequency showed significant difference between MPA high and low exposure groups(66.7%vs 15.4%,P=0.013,OR=2.526).T allele frequency was marginally higher in MPA high exposure group than that in low exposure group(83.3%vs 53.3%,P=0.072).Conclusion TT genotype on 1236 of MDR1 indicates a risk of early high exposure to MPA in Chinese renal transplant patients given by oral MMF,