Meta-analysis of the associations of IMPDH and UGT1A9 polymorphisms with rejection in kidney transplant recipients taking mycophenolic acid

Abstract

Purpose: To investigate the associations of IMPDH and UGT1A9 polymorphisms with rejection in kidney transplant recipients taking mycophenolic acid (MPA).

Methods: PubMed, Web of Science, Embase, Cochrane Library, Wanfang Data, and the China Academic Journal Network Publishing Database were systematically searched for studies investigating the associations of IMPDH1, IMPDH2, and UGT1A9 polymorphisms with rejection in kidney transplant recipients taking MPA. Associations were evaluated by pooled odds ratios (ORs) and effect sizes (ESs) with 95% confidence intervals (CIs).

Results: Twelve studies were included in the analysis, including a total of 2342 kidney transplant recipients. The results showed that compared with the TC + CC variant genotypes, the TT genotype of IMPDH2 3757 T > C was significantly associated with a higher risk of rejection (ES = 1.60, 95% CI = 1.07-2.40, P = 0.021), while there was no significant association of the IMPDH2 3757 T > C polymorphism with acute rejection within 1 year in kidney transplant recipients (OR = 1.49, 95% CI = 0.79-2.80, P = 0.217; ES = 1.44, 95% CI = 0.88-2.36, P = 0.142). The GG genotypes of IMPDH1 125G > A and IMPDH1 106G > A were significantly associated with a higher risk of rejection (ES = 1.91, 95% CI = 1.11-3.28, P = 0.019) and acute rejection within 1 year (ES = 2.12, 95% CI = 1.45-3.10, P < 0.001) than the variant genotypes GA + AA. The TT genotype of UGT1A9 275 T > A showed a decreased risk of rejection compared with the variant genotypes TA + AA (ES = 0.44, 95% CI = 0.23-0.84, P = 0.013).

Conclusions: IMPDH1, IMPDH2, and UGT1A9 polymorphisms were associated with rejection in kidney transplant recipients, and the genetic backgrounds of patients should be considered when using MPA.

Keywords: IMPDH1; IMPDH2; Kidney transplant; Meta-analysis; Mycophenolic acid; Polymorphism; UGT1A9.