Relationship between SLCO1B1 polymorphisms and methotrexate intolerance in Mexican children with juvenile idiopathic arthritis.

IF 2.9 3区医学 Q2 RHEUMATOLOGY

Clinical Rheumatology Pub Date : 2024-11-04 DOI:10.1007/s10067-024-07221-x

Jimena Garcia-Silva, Beatriz Silva-Ramirez, Ana V Villarreal-Treviño, Viviana Mata-Tijerina, Nadina E Rubio-Perez, Fernando Garcia-Rodriguez

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引用次数: 0

Abstract

Introduction: The most frequent adverse events (AEs) of methotrexate (MTX) are gastrointestinal symptoms and hepatotoxicity, which can affect its adherence, leading to reduced effectiveness. The SLCO1B1 gene codes for a liver protein (OATP1B1) responsible for drug transportation. Genetic variations within the SLCO1B1 gene locus impact drug transport, leading to altered pharmacokinetic profiles, delayed MTX clearance, and increased risk of toxicity. This study aimed to determine the association between single nucleotide polymorphisms (SNPs) in the SLCO1B1 gene (rs4149056, rs2306283) with the development of AEs in patients with juvenile idiopathic arthritis (JIA) treated with MTX.

Method: We performed an observational retrospective study to analyze the relationship between SNPs in the SLCO1B1 gene and the development of AEs in pediatric patients treated with MTX for JIA.

Results: Thirty patients with JIA were included, 22 females (73.3%), with a median age of 11 years (IQR 8.3-15). The most frequent JIA subtype was rheumatoid factor-positive polyarthritis (36.7%). Twenty patients (66.7%) reported AEs. The *1B haplotype was the most frequent in this group (53.3%) and conferred a higher risk of developing AEs (OR = 3.89, 95% CI = 1.23 -12.29, p = 0.03).

Conclusions: Patients with the allele *1B may benefit from lower doses of MTX. SLCO1B1 genotyping is a promising technique to identify patients at higher risk of AEs during treatment with MTX, thus requiring dose optimization.

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墨西哥幼年特发性关节炎患儿的 SLCO1B1 多态性与甲氨蝶呤不耐受性之间的关系。

简介：甲氨蝶呤（MTX）最常见的不良反应（AEs）是胃肠道症状和肝毒性，这可能会影响服药依从性，导致疗效降低。SLCO1B1 基因编码一种负责药物运输的肝脏蛋白（OATP1B1）。SLCO1B1 基因位点内的遗传变异会影响药物转运，导致药代动力学特征改变、MTX 清除延迟和毒性风险增加。本研究旨在确定SLCO1B1基因中的单核苷酸多态性（SNPs）（rs4149056、rs2306283）与接受MTX治疗的幼年特发性关节炎（JIA）患者发生AEs之间的关系：我们进行了一项观察性回顾研究，以分析SLCO1B1基因中的SNPs与接受MTX治疗的幼年特发性关节炎（JIA）患者发生AEs的关系：研究共纳入了 30 名 JIA 患者，其中 22 名女性（73.3%），中位年龄为 11 岁（IQR 8.3-15）。最常见的 JIA 亚型是类风湿因子阳性多关节炎（36.7%）。20名患者（66.7%）报告了AEs。*1B 单倍型在该组中最常见（53.3%），并带来更高的发生 AE 的风险（OR = 3.89，95% CI = 1.23 -12.29，p = 0.03）：结论：等位基因*1B的患者可能会从较低剂量的MTX中获益。SLCO1B1基因分型是一项很有前景的技术，可用于识别在使用MTX治疗期间出现AEs风险较高的患者，从而优化剂量。

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

Clinical Rheumatology 医学-风湿病学

CiteScore

6.90

自引率

2.90%

发文量

441

审稿时长

3 months

期刊介绍： Clinical Rheumatology is an international English-language journal devoted to publishing original clinical investigation and research in the general field of rheumatology with accent on clinical aspects at postgraduate level. The journal succeeds Acta Rheumatologica Belgica, originally founded in 1945 as the official journal of the Belgian Rheumatology Society. Clinical Rheumatology aims to cover all modern trends in clinical and experimental research as well as the management and evaluation of diagnostic and treatment procedures connected with the inflammatory, immunologic, metabolic, genetic and degenerative soft and hard connective tissue diseases.