Effect of UGT1A6 and UGT2B7 polymorphisms on the valproic acid serum concentration and drug-induced liver injury.

IF 1.9 4区医学 Q3 PHARMACOLOGY & PHARMACY Pharmacogenomics Pub Date : 2024-11-20 DOI:10.1080/14622416.2024.2409061

Mengchen Yu, Yan Zhao, Fan Zhou, Weiliang Li, Jing Liu, Linlin Zhao, Zhirui Song, Ling Tong, Ying Zhang, Yajuan Wang, Shenglan Shang, Airong Yu

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Abstract

Aim: Valproic acid (VPA) is a classic broad-spectrum antiepileptic drug, with significant pharmacokinetic variability. Genetic polymorphisms contribute to this variability, influencing both VPA trough serum concentration (VPA concentration) and VPA-induced liver injury. Our study aims to investigate the association between polymorphisms of uridine diphosphate glucuronyl transferase (UGT) 1A6, UGT2B7 and VPA concentration and screen for potential genetic loci affecting VPA-induced liver injury.Methods: This study included epilepsy patients treated with VPA. PCR-RFLP method was used to determine the genotypes of UGT1A6 and UGT2B7. Chemiluminescent microparticle immunoassay was used to measure VPA concentration. Multiple linear regression and logistic regression were employed to analyze factors influencing VPA concentration and VPA-induced liver injury, respectively.Results: The correlation between UGT polymorphism and VPA concentration was analyzed in 133 samples. For VPA-induced liver injury, 105 patients were analyzed, with 29 in the liver injury group and 76 in the control group. Our finding showed patients with the UGT1A6-T19G variant had significantly lower VPA concentrations compared with wild-type patients and UGT1A6-T19G, A541G, A552C and UGT2B7-C802T, G211T, A268G polymorphisms showed no impact on VPA-induced liver injury.Conclusion: This study demonstrated UGT1A6-T19G polymorphisms affected the VPA concentration, providing a theoretical basis for the individualized clinical use of VPA.

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UGT1A6 和 UGT2B7 多态性对丙戊酸血清浓度和药物性肝损伤的影响

目的：丙戊酸（VPA）是一种典型的广谱抗癫痫药物，具有显著的药代动力学变异性。遗传多态性是造成这种变异性的原因之一，它影响着 VPA 的血清谷浓度（VPA 浓度）和 VPA 引起的肝损伤。我们的研究旨在调查二磷酸尿苷葡萄糖醛酸转移酶（UGT）1A6、UGT2B7的多态性与VPA浓度之间的关系，并筛选影响VPA诱导肝损伤的潜在遗传位点：本研究纳入了接受VPA治疗的癫痫患者。采用 PCR-RFLP 方法测定 UGT1A6 和 UGT2B7 的基因型。采用化学发光微粒子免疫测定法测定 VPA 浓度。分别采用多元线性回归和逻辑回归分析VPA浓度和VPA诱导肝损伤的影响因素：结果：分析了 133 份样本中 UGT 多态性与 VPA 浓度之间的相关性。分析了 105 例 VPA 引起的肝损伤患者，其中肝损伤组 29 例，对照组 76 例。我们的研究结果表明，与野生型患者相比，UGT1A6-T19G变异型患者的VPA浓度明显较低，而UGT1A6-T19G、A541G、A552C和UGT2B7-C802T、G211T、A268G多态性对VPA诱导的肝损伤没有影响：本研究表明，UGT1A6-T19G 多态性会影响 VPA 的浓度，这为临床个体化使用 VPA 提供了理论依据。

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来源期刊

Pharmacogenomics 医学-药学

CiteScore

3.40

自引率

9.50%

发文量

审稿时长

4-8 weeks

期刊介绍： Pharmacogenomics (ISSN 1462-2416) is a peer-reviewed journal presenting reviews and reports by the researchers and decision-makers closely involved in this rapidly developing area. Key objectives are to provide the community with an essential resource for keeping abreast of the latest developments in all areas of this exciting field. Pharmacogenomics is the leading source of commentary and analysis, bringing you the highest quality expert analyses from corporate and academic opinion leaders in the field.