单磷酸肌苷脱氢酶 2 型多态性 IMPDH2 3757T>C (rs11706052) 与使用霉酚酸类免疫抑制剂的肾移植受者 12 个月的移植物功能变化。

IF 2.9 3区医学 Q2 GENETICS & HEREDITY

Pharmacogenomics Journal Pub Date : 2024-05-20 DOI:10.1038/s41397-024-00335-0

Luka Penezić, Sandra Nađ-Škegro, Ayla Hadžavdić, Lana Ganoci, Željko Kaštelan, Vladimir Trkulja, Nada Božina

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引用次数: 0

摘要

单磷酸肌苷脱氢酶 2 型多态性 IMPDH2 3757T>C 的变异等位基因与体外酶活性增加和对霉酚酸（MPA）的敏感性降低有关。有研究表明，在使用基于 MPA 的免疫抑制剂的肾移植受者中，该基因与急性排斥反应风险增加有关，但并不明确。我们评估了移植变异等位基因携带者和野生型受试者一年的估计肾小球滤过率（eGFR）的变化情况，同时控制了一些人口统计学、药物遗传学、（并发）发病率、治疗基线和时变协变量。在52名变异基因携带者和202名野生型对照组中，到第28天的eGFR斜率（GMR = 1.01，95% CI 0.93-1.09）以及第28天和365天之间的eGFR斜率（GMR = 1.01，95% CI 0.99-1.02）几乎相同。即使在调整了未测量混杂因素的强烈假定影响后，估计值（95%CIs）仍在±20%的差异范围内。IMPDH2 3757T>C 多态性不会影响移植后第一年的肾移植功能。

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Inosine monophosphate dehydrogenase type 2 polymorphism IMPDH2 3757T>C (rs11706052) and 12-month evolution of the graft function in renal transplant recipients on mycophenolate-based immunosuppression

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Variant allele at the inosine monophosphate dehydrogenase type 2 polymorphism IMPDH2 3757T>C has been associated with increased enzyme activity and reduced susceptibility to mycophenolic acid (MPA) in vitro. It has been suggested associated with an increased risk of acute rejection in renal transplant recipients on MPA-based immunosuppression, but not unambiguously. We assessed one-year evolution of the estimated glomerular filtration rate (eGFR) in transplanted variant allele carriers and wild-type subjects, while controlling for a number of demographic, pharmacogenetic, (co)morbidity, and treatment baseline and time-varying covariates. The eGFR slopes to day 28 (GMR = 1.01, 95% CI 0.93–1.09), and between days 28 and 365 (GMR = 1.01, 95% CI 0.99–1.02) were practically identical in 52 variant carriers and 202 wild-type controls. The estimates (95%CIs) remained within the limits of ±20% difference even after adjustment for a strong hypothetical effect of unmeasured confounders. Polymorphism IMPDH2 3757T>C does not affect the renal graft function over the 1st year after transplantation.

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来源期刊

Pharmacogenomics Journal 医学-药学

CiteScore

7.20

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The Pharmacogenomics Journal is a print and electronic journal, which is dedicated to the rapid publication of original research on pharmacogenomics and its clinical applications. Key areas of coverage include: Personalized medicine Effects of genetic variability on drug toxicity and efficacy Identification and functional characterization of polymorphisms relevant to drug action Pharmacodynamic and pharmacokinetic variations and drug efficacy Integration of new developments in the genome project and proteomics into clinical medicine, pharmacology, and therapeutics Clinical applications of genomic science Identification of novel genomic targets for drug development Potential benefits of pharmacogenomics.