Department of Pharmacy, The First Affiliated Hospital of Third Military Medical University (Army Medical University), Chongqing, 400038, China.
Department of Pharmacy, The Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China.
Eur J Clin Pharmacol. 2022 Aug;78(8):1227-1238. doi: 10.1007/s00228-022-03311-4. Epub 2022 May 7.
To investigate the associations of IMPDH and UGT1A9 polymorphisms with rejection in kidney transplant recipients taking mycophenolic acid (MPA).
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).
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).
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.
探讨肌苷单磷酸脱氢酶（IMPDH）和尿苷二磷酸葡萄糖醛酸转移酶 1A9（UGT1A9）多态性与接受霉酚酸（MPA）治疗的肾移植受者排斥反应的关系。
系统检索 PubMed、Web of Science、Embase、Cochrane 图书馆、万方数据和中国学术期刊网络出版数据库，以调查 IMPDH1、IMPDH2 和 UGT1A9 多态性与接受 MPA 治疗的肾移植受者排斥反应之间关系的研究。采用合并优势比（OR）和效应大小（ES）及其 95%置信区间（CI）评估相关性。
分析纳入了 12 项研究，共计 2342 例肾移植受者。结果显示，与 TC+CC 变异基因型相比，IMPDH2 3757T>C 的 TT 基因型与更高的排斥反应风险显著相关（ES=1.60，95%CI=1.07-2.40，P=0.021），而 IMPDH2 3757T>C 多态性与肾移植受者 1 年内急性排斥反应无显著相关性（OR=1.49，95%CI=0.79-2.80，P=0.217；ES=1.44，95%CI=0.88-2.36，P=0.142）。IMPDH1 125G>A 和 IMPDH1 106G>A 的 GG 基因型与更高的排斥反应风险（ES=1.91，95%CI=1.11-3.28，P=0.019）和 1 年内急性排斥反应（ES=2.12，95%CI=1.45-3.10，P<0.001）显著相关，而 GA+AA 变异基因型则无此相关性。与 TA+AA 变异基因型相比，UGT1A9 275T>A 的 TT 基因型发生排斥反应的风险降低（ES=0.44，95%CI=0.23-0.84，P=0.013）。
IMPDH1、IMPDH2 和 UGT1A9 多态性与肾移植受者的排斥反应有关，在使用 MPA 时应考虑患者的遗传背景。
