Association of UGTs, ABCC2, SLCO1B1 and IMPDH Gene Polymorphisms with the Metabolism and Adverse Reactions of Mycophenolate Ester in Renal Transplant Patients
WANG Pei-le1, ZHANG Min2, QU Wei-miao3, ZHANG Xiao-jian1, YANG Jing1
1. Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; 2. Department of Pharmacy, People's Hospital of Zhongmu County, Zhengzhou 451450, China; 3. Department of Drug Administration, People's Hospital of Dancheng County, Zhoukou 477150, China
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.
王培乐, 张敏, 屈惟妙, 张晓坚, 杨晶. UGTs、ABCC2、SLCO1B1和IMPDH基因多态性与肾移植患者霉酚酸酯代谢和不良反应的相关性研究[J]. 中国药学杂志, 2020, 55(10): 849-853.
WANG Pei-le, ZHANG Min, QU Wei-miao, ZHANG Xiao-jian, YANG Jing. Association of UGTs, ABCC2, SLCO1B1 and IMPDH Gene Polymorphisms with the Metabolism and Adverse Reactions of Mycophenolate Ester in Renal Transplant Patients. Chinese Pharmaceutical Journal, 2020, 55(10): 849-853.
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2020, Vol. 55 
