Impact of UGT2B7 and ABCC2 genetic polymorphisms on mycophenolic acid metabolism in Chinese renal transplant recipients

• Published in: Pharmacogenomics Vol. 19; no. 17; pp. 1323 - 1334
• Main Authors: Li, Li-Qing, Chen, Di-Na, Li, Chuan-Jiang, Li, Qing-Ping, Chen, Yan, Fang, Ping, Zheng, Ping, Lu, Hui-Jie, Ye, De-Mei, Wan, Hao-Yang, Li, Jie, Li, Liang
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.11.2018
• Subjects: Adult; Asian Continental Ancestry Group - genetics; Creatinine; Drug dosages; Female; Gene expression; Genetic diversity; Genomes; Genotype; Glucuronosyltransferase - genetics; Health risk assessment; Humans; Influence; Kidney - metabolism; Kidney transplantation; Kidney Transplantation - methods; Male; Metabolism; Metabolites; Multidrug Resistance-Associated Proteins - genetics; Mycophenolic acid; Mycophenolic Acid - metabolism; Pharmacokinetics; Polymorphism; Polymorphism, Single Nucleotide - genetics; Population; Regression analysis; Single-nucleotide polymorphism; Transplant Recipients; Transplants & implants; pharmacokinetics; genetic polymorphisms; mycophenolic acid
• ISSN: 1462-2416; 1744-8042
• DOI: 10.2217/pgs-2018-0114

To evaluate genetic variants affecting mycophenolic acid (MPA) metabolism in Chinese renal transplant recipients. Total 11 SNPs of UGT1A9, UGT1A8, UGT2B7, ABCC2, ABCG2 and SLCO1B3 were genotyped in 408 Chinese renal transplant recipients. Associations between SNPs and MPA concentration/dose ratio (C /D) were analyzed using different genetic models. Multivariate linear regression was used to analyze associations between log (C /D) and clinical factors. Results: After adjustment by clinical factors, UGT2B7 rs7662029 was associated with log (C /D) using a dominant (p = 0.041) and an additive (p = 0.038) model, ABCC2 rs717620 was associated with log (C /D) using a recessive model (p = 0.019). Using additive model, SNP-SNP interactions were identified (p = 0.002) between ABCC2 rs717620 and UGT1A9 rs2741049, with interactions (p = 0.002) between ABCC2 rs717620 and UGT1A8 rs1042597. Age, albumin and serum creatinine were associated with log (C /D). rs7662029 and rs717620 may affect MPA pharmacokinetics. SNP-SNP interactions and clinical factors may have significant effects on MPA metabolism.