GGH intronic variant rs3780130 is associated with methotrexate levels in children with brain tumors

IF 2.7 3区生物学 Q2 GENETICS & HEREDITY

Gene Pub Date : 2026-02-10 Epub Date: 2025-11-29 DOI:10.1016/j.gene.2025.149929

Si-han Liu , Xiao-yan Kong , Miao Li , Shu-mei Wang

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引用次数: 0

Abstract

Background

Pediatric brain tumors (PBTs) are the leading type of solid tumors in children, profoundly affecting both survival rates and quality of life. Methotrexate (MTX) is an essential chemotherapy drug for treating these tumors; however, its efficacy and toxicity vary among patients due to genetic factors.

Objective

This study examined the impact of the intronic rs3780130 polymorphism in the gamma-glutamyl hydrolase (GGH) gene on MTX concentrations and related toxicities in patients with PBTs.

Methods

The GGH rs3780130 T > A polymorphism was genotyped using the Sequenom MassARRAY iPLEX platform in a cohort of 73 PBT patients.

Results

We found that children with the AA genotype had significantly higher MTX concentrations compared to those with TT and TA genotypes (P < 0.05). Additionally, the AA genotype was significantly associated with a higher incidence of hepatotoxicity relative to the TT genotype (P < 0.05). It showed a significantly lower occurrence of gastrointestinal toxicities when compared to the TA genotype (P < 0.05). Bioinformatics analysis revealed that the rs3780130 polymorphism had a significant effect on GGH expression across various tissues, suggesting a potential mechanism by which this variant modulated MTX metabolism.

Conclusion

Our findings highlight the importance of GGH polymorphisms in personalizing MTX therapy for PBT patients and emphasize the necessity for further research to explore the clinical implications of GGH genotypes in larger cohorts, ultimately aiming for more precise therapeutic strategies.

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GGH内含子变异rs3780130与脑肿瘤患儿甲氨蝶呤水平相关

背景：儿童脑肿瘤（PBTs）是儿童实体肿瘤的主要类型，深刻影响着儿童的生存率和生活质量。甲氨蝶呤（MTX）是治疗这些肿瘤的重要化疗药物；然而，由于遗传因素，其疗效和毒性因患者而异。目的：研究γ -谷氨酰水解酶（GGH）基因rs3780130内含子多态性对pbt患者MTX浓度及相关毒性的影响。方法：使用Sequenom MassARRAY iPLEX平台对73例PBT患者的GGH rs3780130 T > A多态性进行基因分型。结果：我们发现AA基因型儿童的MTX浓度明显高于TT和TA基因型儿童（P ）。结论：我们的研究结果强调了GGH多态性对PBT患者个性化MTX治疗的重要性，并强调了进一步研究的必要性，以在更大的队列中探索GGH基因型的临床意义，最终旨在制定更精确的治疗策略。

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

Gene 生物-遗传学

CiteScore

6.10

自引率

2.90%

发文量

718

审稿时长

42 days

期刊介绍： Gene publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses.