Impact of UGT1A4 and UGT2B7 polymorphisms on lamotrigine plasma concentration in patients with bipolar disorder.

IF 1.7 3区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pharmacogenetics and genomics Pub Date : 2024-10-01 Epub Date: 2024-08-23 DOI:10.1097/FPC.0000000000000543

Ting Zhao, Hui-Lan Zhang, Jie Feng, Long Cui, Li Sun, Hong-Jian Li, Lu-Hai Yu

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引用次数: 0

Abstract

Purpose: The purpose of this study was to evaluate the effect of UGT1A4 and UGT2B7 polymorphisms on the plasma concentration of lamotrigine in Chinese patients with bipolar disorder.

Methods: A total of 104 patients were included in this study. Steady-state plasma lamotrigine concentrations were determined in each patient after at least 21 days of continuous treatment with a set dose of the drug. Lamotrigine plasma concentrations were ascertained using ultra-performance liquid chromatography. Simultaneously, plasma samples were used for patient genotyping.

Results: The age, sex, BMI, daily lamotrigine dose, plasma lamotrigine concentration, and lamotrigine concentration/dose ratio of patients exhibited significant differences, and these were associated with differences in the genotype [ UGT1A4 -142T>G and UGT2B7 -161C>T ( P < 0.05)]. Patients with the GG and GT genotypes in UGT1A4 -142T>G had significantly higher lamotrigine concentration/dose values (1.6 ± 1.1 and 1.7 ± 0.5 μg/ml per mg/kg) than those with the TT genotype (1.4 ± 1.1 μg/ml per mg/kg). Likewise, patients with the UGT2B7 -161C>T TT genotype had significantly higher lamotrigine concentration/dose values (1.6 ± 1.1 μg/ml per mg/kg) than those with the CC genotype (1.3 ± 1.3 μg/ml per mg/kg). Multiple linear regression analysis showed that sex, lamotrigine dose, UGT1A4 -142T>G, and UGT2B7 -161C>T were the most important factors influencing lamotrigine pharmacokinetics ( P < 0.001).

Conclusion: The study results suggest that the UGT1A4 -142T>G and UGT2B7 -161C>T polymorphisms affect lamotrigine plasma concentrations in patients with bipolar disorder.

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UGT1A4 和 UGT2B7 多态性对双相情感障碍患者拉莫三嗪血浆浓度的影响。

目的：本研究旨在评估 UGT1A4 和 UGT2B7 多态性对中国双相情感障碍患者拉莫三嗪血浆浓度的影响：本研究共纳入104例患者。方法：本研究共纳入 104 例患者，每例患者在接受至少 21 天的固定剂量拉莫三嗪连续治疗后，测定其血浆中拉莫三嗪的稳态浓度。拉莫三嗪的血浆浓度采用超高效液相色谱法测定。同时，血浆样本还用于患者基因分型：结果：患者的年龄、性别、体重指数、每日拉莫三嗪剂量、血浆拉莫三嗪浓度和拉莫三嗪浓度/剂量比均存在显著差异，这些差异与基因型的不同有关[UGT1A4 -142T>G和UGT2B7 -161C>T（P G的拉莫三嗪浓度/剂量值明显更高（1.6 ± 1.1 和 1.7 ± 0.5 μg/ml per mg/kg）。同样，UGT2B7 -161C>T TT 基因型患者的拉莫三嗪浓度/剂量值（每 mg/kg 1.6 ± 1.1 μg/ml）也明显高于 CC 基因型患者（每 mg/kg 1.3 ± 1.3 μg/ml）。多元线性回归分析表明，性别、拉莫三嗪剂量、UGT1A4 -142T>G和UGT2B7 -161C>T是影响拉莫三嗪药代动力学的最重要因素（P 结论：UGT1A4 -142T>G和UGT2B7 -161C>T是影响拉莫三嗪药代动力学的最重要因素：研究结果表明，UGT1A4 -142T>G和UGT2B7 -161C>T多态性会影响双相情感障碍患者的拉莫三嗪血浆浓度。

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

Pharmacogenetics and genomics 医学-生物工程与应用微生物

CiteScore

3.20

自引率

3.80%

发文量

审稿时长

3 months

期刊介绍： Pharmacogenetics and Genomics is devoted to the rapid publication of research papers, brief review articles and short communications on genetic determinants in response to drugs and other chemicals in humans and animals. The Journal brings together papers from the entire spectrum of biomedical research and science, including biochemistry, bioinformatics, clinical pharmacology, clinical pharmacy, epidemiology, genetics, genomics, molecular biology, pharmacology, pharmaceutical sciences, and toxicology. Under a single cover, the Journal provides a forum for all aspects of the genetics and genomics of host response to exogenous chemicals: from the gene to the clinic.