Influence of UDP-glucuronosyltransferase polymorphisms on mycophenolate mofetil-induced side effects in kidney transplant patients
Influence of UDP-glucuronosyltransferase polymorphisms on mycophenolate mofetil-induced side effects in kidney transplant patients
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DOI：
10.1016/j.transproceed.2008.03.007
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发表时间：
2008-04-01
影响因子：
0.9
通讯作者：
Pavarino-Bertelli, E. C.
中科院分区：
文献类型：
--
作者：
Betnoico, G. N.;Abbud-Filho, M.;Pavarino-Bertelli, E. C.
吗替麦考酚酯 (MMF) 是一种被批准用于移植的免疫抑制前药。其活性代谢物麦考酚酸主要由UDP-葡萄糖醛酸基转移酶（UGT）代谢。在这项研究中，我们回顾性分析了 74 名肾移植患者，他们在免疫抑制方案中服用了 MMF。 UGT1A8 的多态性（-999C > T、密码子 255A > G、密码子 277G > A）与腹泻、血液疾病和感染等副作用的发生相关。在携带变异 UGT1A8 密码子 277A (P = .031)、单倍型 UGT1A8H5 (-999C/密码子 55A/密码子 277A；P = .02) 和双倍型 UGT1A8H2/H5 (-999CC/密码子) 的接受 MMF (2 g/d) 的个体中，感染发作的频率更高 255AA/密码子277GA； P = .015)。这项研究的分子数据表明，UGT 多态性可能是影响接受 MMF 移植治疗的患者临床结果的一个因素；然而，需要进行更大规模的研究。
Mycophenolate mofetil (MMF) is an immunosuppressive prodrug approved for use in transplantation. Its active metabolite, mycophenolic acid, is mainly metabolized by UDP-glucuronosyltransferase (UGT) enzymes. In this study, we retrospectively analyzed 74 kidney transplant patients who had been prescribed MMF as part of their immunosuppression regimen. Polymorphisms in UGT1A8 (-999C > T, codon 255A > G, codon 277G > A) were correlated with the occurrence of side effects, such as diarrhea, blood disorders, and infections. The infectious episodes were more frequently observed among individuals receiving MMF (2 g/d) who carryied the variant UGT1A8 codon 277A (P = .031), the haplotype UGT1A8H5 (-999C/codon 55A/codon 277A; P = .02), and the diplotype UGT1A8H2/H5 (-999CC/codon 255AA/codon 277GA; P = .015). The molecular data from this study suggest that UGT polymorphisms may be a factor influencing clinical outcomes among patients receiving MMF for transplant therapy; however, larger studies are warranted.