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Pharmacogenomics. 2018 Nov;19(17):1323-1334. doi: 10.2217/pgs-2018-0114. Epub 2018 Oct 22.

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

Author information

1
Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, PR China.
2
Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, PR China.
3
Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, PR China.
4
Key Laboratory of single cell technology and application in Guangzhou, Guangdong, PR China.

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

PMID:
30345879
DOI:
10.2217/pgs-2018-0114

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