The immunosuppressant mycophenolic acid (MPA), derived from the prodrug mycophenolate mofetil (MMF), is a drug used widely by kidney transplant recipients. This drug selectively inhibits inosine monophosphate dehydrogenase that controls the proliferation of lymphocytes, aiding in the prevention of rejection of the transplanted organ. Polymorphisms in key genes involved in MMF metabolism may alter the function of the enzymes encoded by them and contribute to interindividual variability in the response to the drug and its efficacy. The aim of this study was to investigate the association of nine polymorphic variants of eight genes involved in MMF pharmacokinetics, with rejection and adverse effects exhibited by kidney transplant recipients who use this drug. Our sample comprised 145 kidney transplant recipients undergoing post-transplant treatment whose immunosuppressive therapy consisted of MMF and corticosteroid combined or not with a calcineurin inhibitor or mTOR inhibitor. The average age of the patients was 46.9 ± 12.5 years, and they underwent transplantation 7 ± 5.71 years ago. The combination of the T/C and C/C genotypes of the polymorphism rs11706052 (IMPDH2) was associated with a 4.2-fold protection, and the combination of the genotypes A/G and G/G of the polymorphism rs7438135 (UGT2B7) showed a 2.4-fold protection, against rejection. The association of T/C and C/C genotypes in the SNP rs11706052 (IMPDH2) with the occurrence of rejection episodes considering only patients who received immunosuppressive drug MMF associated with cyclosporine or tacrolimus and corticoids, demonstrated association with a protection against rejection 15.6-fold. The T/T genotype of the polymorphism rs2241409 (CES2) was associated with a 7.2-fold increased risk of rejection. Therefore, these polymorphisms that showed a strong association with rejection episodes should be considered in future studies on new prognostic markers for rejection in patients treated with MMF.

中文翻译：

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IMPDH2，UGT2B7和CES2基因中的多态性影响接受麦考酚酸酯的肾移植受者的移植排斥风险。

源自麦考酚酸酯前药（MMF）的免疫抑制剂麦考酚酸（MPA）是肾移植受者广泛使用的药物。该药物选择性抑制肌苷一磷酸脱氢酶，后者可控制淋巴细胞的增殖，有助于预防移植器官的排斥反应。MMF代谢中涉及的关键基因的多态性可能会改变它们编码的酶的功能，并导致对药物反应及其功效的个体差异。这项研究的目的是调查参与MMF药代动力学的8个基因的9个多态变异与使用该药的肾脏移植受者表现出的排斥反应和不良反应之间的关系。我们的样本包括145位接受移植后治疗的肾移植受者，其免疫抑制治疗包括MMF和皮质类固醇与钙调神经磷酸酶抑制剂或mTOR抑制剂联合或不联合。患者的平均年龄为46.9±12.5岁，他们在7±5.71年前接受了移植。rs11706052（IMPDH2）多态性的T / C和C / C基因型的组合与4.2倍的保护相关，而rs7438135（UGT2B7）多态性的基因型A / G和G / G的组合显示2.4倍保护，防止拒收。SNP rs11706052（IMPDH2）中的T / C和C / C基因型与排斥反应的发生相关，仅考虑接受与环孢霉素或他克莫司和皮质类固醇相关的免疫抑制药物MMF的患者，证明与15.6倍拒绝反应的保护相关。rs2241409（CES2）多态性的T / T基因型与排斥风险增加7.2倍有关。因此，这些与多发性排斥反应密切相关的多态性应在以后的MMF治疗患者新的预后标志研究中考虑。