The pharmacogenetics of tacrolimus in renal transplant patients: association with tremors, new-onset diabetes and other clinical events

IF 2.9 3区医学 Q2 GENETICS & HEREDITY

Pharmacogenomics Journal Pub Date : 2024-01-22 DOI:10.1038/s41397-024-00323-4

Amani Abderahmene, Yassine khalij, Amira Moussa, Meriam Ammar, Amel Ellouz, Dorra Amor, Houwaida Abbes, Mohamed Rayen Ganouni, Wissal Sahtout, Saoussen Chouchene, Asma omezzine, Dorsaf zellama, Ali Bouslama

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引用次数: 0

Abstract

Our study is the first study to investigate the effect of SNPs in CYP3A5, CYP3A4, ABCB1 and POR genes on the incidence of tremors, nephrotoxicity, and diabetes mellitus. A total of 223 renal transplant patients receiving tacrolimus and mycophenolate mofetil (MMF) were recruited. Both adults and children patients participated in the study. Genotyping was performed using PROFLEX-PCR followed by RFLP. MPA and tacrolimus plasma concentrations were measured by immunoassay. The AUC0-12h of MMF was estimated by a Bayesian method. We found a statistically significant association between the CYP3A5*3 and CYP3A4*1B genotypes and the tacrolimus exposure. We found a lower occurrence of nephrotoxicity (p = 0.03), tremor (p = 0.01), and new-onset diabetes (p = 0.002) associated with CYP3A5*1 allele. The CYP3A4*1B allele was significantly associated with a lower occurrence of new-onset diabetes (p = 0.026). The CYP3A5*1 allele was significantly associated with an increased risk of acute and chronic rejection (p = 0.03 and p < 0.001, respectively). Our results support the usefulness of tacrolimus pharmacokinetics in pre-kidney transplant assessments.

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肾移植患者他克莫司的药物遗传学：与震颤、新发糖尿病和其他临床事件的关系

我们的研究是首次调查 CYP3A5、CYP3A4、ABCB1 和 POR 基因中的 SNPs 对震颤、肾毒性和糖尿病发病率影响的研究。研究共招募了 223 名接受他克莫司和霉酚酸酯（MMF）治疗的肾移植患者。成人和儿童患者均参与了研究。基因分型是通过 PROFLEX-PCR 和 RFLP 进行的。MPA 和他克莫司的血浆浓度通过免疫测定法测定。MMF 的 AUC0-12h 用贝叶斯法估算。我们发现 CYP3A5*3 和 CYP3A4*1B 基因型与他克莫司的暴露量之间存在统计学意义上的显著关联。我们发现，与 CYP3A5*1 等位基因相关的肾毒性（p = 0.03）、震颤（p = 0.01）和新发糖尿病（p = 0.002）发生率较低。CYP3A4*1B 等位基因与较低的新发糖尿病发病率（p = 0.026）显著相关。CYP3A5*1 等位基因与急性和慢性排斥反应风险的增加明显相关（分别为 p = 0.03 和 p <0.001）。我们的研究结果支持他克莫司药代动力学在肾移植前评估中的作用。

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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.