Association of UGTs, ABCC2, SLCO1B1 and IMPDH Gene Polymorphisms with the Metabolism and Adverse Reactions of Mycophenolate Ester in Renal Transplant Patients / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the association of UGTs, ABCC2, SLCO1B1 and IMPDH gene polymorphisms with metabolism and adverse reaction of mycophenolate ester in early renal transplant recipients. METHODS: A total of 233 patients who received tacrolimus+glucocorticoid+mycophenolate mofetil treatment after living kidney transplantation were enrolled. Single nucleotide polymorphisms of 13 gene were detected by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Kruskal-Wallis H test was used to analyze the effect of 13 single nucleotide polymorphisms on the exposure/dose (AUC/D) and adverse reactions of mycophenolic acid in early recipients after renal transplantation. RESULTS: The AUC/D of mycophenolic acid in UGT2B7 802C>T CC and CT genotype recipients was (36.03±16.19) and (38.06±15.41) mg•h•L-1/g•d-1, which was significantly lower than that in TT genotype recipients (43.63±15.10) mg•h•L-1/g•d-1 (P=0.021). The AUC/D of mycophenolic acid in SLCO1B1 521T > C TT, TC and CC genotype recipients were (36.78±15.70), (41.27±12.92) and (45.10±21.32) mg•h•L-1/g•d-1, respectively. There was significant difference between groups (P=0.036). There was no significant difference between 13 single nucleotide polymorphisms and adverse reactions (P>0.05). CONCLUSION: The AUC/D of mycophenolic acid in early recipients after kidney transplantation are associated with the polymorphism of UGT2B7 802C > T and SLCO1B1 521T > C.