Association of SLC19A1 Gene Polymorphisms and Its Regulatory miRNAs with Methotrexate Toxicity in Children with Acute Lymphoblastic Leukemia.

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Issues in Molecular Biology Pub Date : 2024-10-16 DOI:10.3390/cimb46100685

Vasiliki Karpa, Kallirhoe Kalinderi, Eleni Gavriilaki, Vasiliki Antari, Emmanuil Hatzipantelis, Theodora Katopodi, Liana Fidani, Athanasios Tragiannidis

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引用次数: 0

Abstract

Methotrexate (MTX) is an anti-folate chemotherapeutic agent that is considered to be a gold standard in Acute Lymphoblastic Leukemia (ALL) therapy. Nevertheless, toxicities induced mainly due to high doses of MTX are still a challenge for clinical practice. MTX pharmacogenetics implicate various genes as predictors of MTX toxicity, especially those that participate in MTX intake like solute carrier family 19 member 1 (SLC19A1). The aim of the present study was to evaluate the association between SLC19A1 polymorphisms and its regulatory miRNAs with MTX toxicity in children with ALL. A total of 86 children with ALL were included in this study and were all genotyped for rs2838958, rs1051266 and rs1131596 SLC19A1 polymorphisms as well as the rs56292801 polymorphism of miR-5189. Patients were followed up (48, 72 and 96 h) after treatment with MTX in order to evaluate the presence of MTX-associated adverse events. Our results indicate that there is a statistically significant correlation between the rs1131596 SLC19A1 polymorphism and the development of MTX-induced hepatotoxicity (p = 0.03), but there is no significant association between any of the studied polymorphisms and mucositis or other side effects, such as nausea, emesis, diarrhea, neutropenia, skin rash and infections. In addition, when genotype TT of rs1131596 and genotype AA of rs56292801 are both present in a patient then there is a higher risk of developing severe hepatotoxicity (p = 0.0104).

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急性淋巴细胞白血病患儿 SLC19A1 基因多态性及其调控 miRNA 与甲氨蝶呤毒性的关系

甲氨蝶呤（MTX）是一种抗叶酸化疗药物，被认为是急性淋巴细胞白血病（ALL）治疗的金标准。然而，主要由大剂量MTX引起的毒性仍是临床实践中的一项挑战。MTX药物遗传学表明，多种基因可预测MTX的毒性，尤其是那些参与MTX摄入的基因，如溶质运载家族19成员1（SLC19A1）。本研究旨在评估SLC19A1多态性及其调控miRNA与ALL患儿MTX毒性之间的关系。本研究共纳入了86名ALL患儿，并对所有患儿进行了rs2838958、rs1051266和rs1131596 SLC19A1多态性以及miR-5189的rs56292801多态性基因分型。在使用 MTX 治疗后对患者进行了随访（48、72 和 96 h），以评估 MTX 相关不良事件的发生情况。我们的研究结果表明，rs1131596 SLC19A1 多态性与 MTX 诱导的肝毒性之间存在统计学意义上的显著相关性（p = 0.03），但所研究的任何多态性与粘膜炎或其他副作用（如恶心、呕吐、腹泻、中性粒细胞减少、皮疹和感染）之间均无显著相关性。此外，如果患者体内同时存在 rs1131596 的 TT 基因型和 rs56292801 的 AA 基因型，则出现严重肝毒性的风险较高（p = 0.0104）。

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来源期刊

Current Issues in Molecular Biology 生物-生化研究方法

CiteScore

2.90

自引率

3.20%

发文量

380

审稿时长

>12 weeks

期刊介绍： Current Issues in Molecular Biology (CIMB) is a peer-reviewed journal publishing review articles and minireviews in all areas of molecular biology and microbiology. Submitted articles are subject to an Article Processing Charge (APC) and are open access immediately upon publication. All manuscripts undergo a peer-review process.