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Impact of UGT1A9, UGT1A8, UGT2B7, ABCC2, ABCG2 and SLCO1B3 genetic polymorphisms on mycophenolic acid metabolism in Chinese renal transplant recipients

Li-qing Li  Di-na Chen  Chuan-jiang Li  Qing-ping Li  Yan Chen  Ping Fang  Ping Zheng  Hui-jie Lu  De-mei Ye  Hao-yang Wan  Jie Li  Liang Li  
【摘要】:Mycophenolate mofetil(MMF) is an immunosuppressive drug used with organ transplant recipients. The active metabolite of MMF is mycophenolic acid(MPA), which has considerable interpatient variability in its pharmacokinetics. Genetic variants may be important in this variability. This study evaluated genetic variants affecting MPA metabolism in Chinese renal transplant recipients. A retrospective study of 408 Chinese renal transplant recipients receiving MMF as an immunosuppressive drug was conducted. Eleven single nucleotide polymorphisms(SNPs) of UGT1 A9, UGT1 A8, UGT2 B7, ABCC2, ABCG2, and SLCO1 B3 were genotyped with the high resolution melting assay. Associations between each SNP and MPA concentration/dose ratio(C0/D) were analyzed using different genetic models. Pearson correlation was used to analyze associations between C0/D and clinical factors. UGT2 B7 rs7662029 genotype was associated with MPA C0/D using a dominant(p = 0.024) and an additive model(p = 0.028). ABCC2 rs717620 genotype was associated with C0/D using a recessive model(p = 0.043). Using the additive model, SNP-SNP interactions were identified(p = 0.002) between ABCC2 rs717620 and UGT1 A9 rs2741049 with similar interactions(p = 0.002) between ABCC2 rs717620 and UGT1 A8 rs1042597. Age, weight, hematocrit, hemoglobin, albumin and direct bilirubin were significantly associated with MPA C0/D. UGT2 B7 rs7662029 and ABCC2 rs717620 might be SNPs that affect MPA pharmacokinetics in Chinese renal transplant recipients. SNP-SNP interactions and clinical factors may have significant effects on MPA metabolism.

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