Impact of UGT2B7 and ABCC2 Genetic Polymorphisms on Mycophenolic Acid Metabolism in Chinese Renal Transplant Recipients

Abstract

Aim: To evaluate genetic variants affecting mycophenolic acid (MPA) metabolism in Chinese renal transplant recipients. Methods: 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 (C₀/D) were analyzed using different genetic models. Multivariate linear regression was used to analyze associations between log (C₀/D) and clinical factors. Results: After adjustment by clinical factors, UGT2B7 rs7662029 was associated with log (C₀/D) using a dominant (p = 0.041) and an additive (p = 0.038) model, ABCC2 rs717620 was associated with log (C₀/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 (C₀/D). Conclusion: rs7662029 and rs717620 may affect MPA pharmacokinetics. SNP–SNP interactions and clinical factors may have significant effects on MPA metabolism.

Keywords::

• genetic polymorphisms
• mycophenolic acid
• pharmacokinetics

Supplementary data

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https://www.tandfonline.com/doi/suppl/10.2217/pgs-2018-0114

Financial & competing interests disclosure

This work was supported by the Natural Science Fund of Guangdong, China (2015A030313306), the Research Fund for the Distinguished Young Teachers to Liang Li of Southern Medical University, the Innovation Promotion Program of Southern Medical University (CX2015N011) and Southern Medical University Innovation Training Program for Undergraduate Students (201712121005 & 201812121005). The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by the Natural Science Fund of Guangdong, China (2015A030313306), the Research Fund for the Distinguished Young Teachers to Liang Li of Southern Medical University, the Innovation Promotion Program of Southern Medical University (CX2015N011) and Southern Medical University Innovation Training Program for Undergraduate Students (201712121005 & 201812121005). The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript