Association of CYP3A5 rs15524 and CYP3A7 rs776744 polymorphisms on tac IPV and clinical outcomes in early post-heart transplantation.

IF 2 4区医学 Q3 GENETICS & HEREDITY

BMC Medical Genomics Pub Date : 2025-10-07 DOI:10.1186/s12920-025-02231-3

Yuhui Chai, Lili Hu, Yiping Zhu, Danni Quan, Yuhong Li, Xuebin Wang, Yunyun Yang, Zhuo Wang

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Abstract

Background: The intrapatient variability (IPV) of tacrolimus (Tac) has gradually become a new index for the prognosis of organ transplantation. The gene polymorphism is involved in the pharmacokinetic process of Tac. The aim of this study was to investigate the effects of genetic polymorphisms on Tac IPV and other clinical outcomes in heart transplant recipients during the early post-transplantation period.

Methods: Our study retrospectively collected the clinical data and genotyping results of 48 heart transplant recipients. SPSS (21.0) and Graphpad Prism (8.0) were used to analyze the effect of gene polymorphism on Tac concentration (C₀) and clinical outcome.

Results: The CYP3A5 rs15524 AA genotype has a higher trough concentrations/dose (C₀/D) value than G allele carriers, and CYP3A7 rs776744 CC genotype has a higher C₀/D value than T allele carriers. Patients with The CYP3A5 rs15524 and CYP3A7 rs776744 mutants had a higher IPV. One year after heart transplantation, the mortality of wild-type and mutant CYP3A5 rs15524 patients due to rejection was 0 vs. 10.7% (P = 0.255). The mortality caused by rejection in wild-type patients and mutant patients of CYP3A7 rs776744 was 4.5% vs. 7.7% (p = 0.564).

Conclusions: Genetic polymorphisms of CYP3A5 rs15524 and CYP3A7 rs776744 affect tacrolimus metabolism in heart transplant recipients, significantly affecting Tac C₀/D during the early postoperative period. In addition, gene polymorphism may be related to Tac IPV and clinical outcome in patients with early heart transplantation.

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CYP3A5 rs15524和CYP3A7 rs776744多态性与早期心脏移植后tac IPV和临床结局的关系

背景：他克莫司（Tac）的患者内变异性（IPV）逐渐成为器官移植预后的新指标。基因多态性参与了Tac的药代动力学过程。本研究的目的是研究遗传多态性对心脏移植受者移植后早期Tac IPV和其他临床结果的影响。方法：回顾性收集48例心脏移植受者的临床资料和基因分型结果。采用SPSS（21.0）软件和Graphpad Prism（8.0）软件分析基因多态性对Tac浓度（C0）及临床预后的影响。结果：CYP3A5 rs15524 AA基因型的谷浓度/剂量（C0/D）值高于G等位基因携带者，CYP3A7 rs776744 CC基因型的C0/D值高于T等位基因携带者。CYP3A5 rs15524和CYP3A7 rs776744突变体患者的IPV更高。心脏移植后1年，野生型和突变型CYP3A5 rs15524患者因排斥反应的死亡率分别为0和10.7% （P = 0.255）。CYP3A7 rs776744野生型和突变型患者排斥反应死亡率分别为4.5%和7.7% （p = 0.564）。结论：CYP3A5 rs15524和CYP3A7 rs776744基因多态性影响心脏移植受者他克莫司代谢，显著影响术后早期Tac C0/D。此外，基因多态性可能与早期心脏移植患者的Tac IPV和临床结局有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BMC Medical Genomics 医学-遗传学

CiteScore

3.90

自引率

0.00%

发文量

243

审稿时长

3.5 months

期刊介绍： BMC Medical Genomics is an open access journal publishing original peer-reviewed research articles in all aspects of functional genomics, genome structure, genome-scale population genetics, epigenomics, proteomics, systems analysis, and pharmacogenomics in relation to human health and disease.