Magadmi Rania, Alharthi Ahlam M, Alqurashi Lina A, Jali Ibtisam M, Sharawi Zeina W, Jamal Maha H, Bawazir Yasser, Mustafa Mohammad, Bahlas Sami M, Jamal Basma T, Daghasi Hassan, Altowairqi Abdulrahman S, Al Shaer Dalal Sameer
Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Department of Biological Sciences, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia.
Pharmaceuticals (Basel). 2025 Jul 20;18(7):1069. doi: 10.3390/ph18071069.
Methotrexate (MTX) remains the most commonly prescribed drug used to treat rheumatoid arthritis (RA). Polymorphisms in solute carrier organic anion transporter family member 1B3 () and may play a critical role in MTX pharmacokinetics and patient outcomes. However, research on these polymorphisms in Saudi Arabia remains limited. We evaluated the association of (rs4149117, rs7311358) and (rs2306283, rs4149056) polymorphisms with MTX efficacy and safety in Saudi patients with RA. This multicenter, case-control study included patients diagnosed with RA in Jeddah and Taif. Demographic and clinical data were collected and analyzed. Genotyping of (rs4149117, rs7311358) and (rs2306283, rs4149056) polymorphisms was performed using Sanger sequencing. Statistical analyses, including logistic regression and haplotype analysis, were conducted to evaluate associations between these polymorphisms, MTX efficacy, and toxicity. The study cohort comprised 100 patients with RA, with 46 showing a good response to MTX and 54 showing a poor response. Clinical predictors of MTX response were significantly higher in patients with poor response. Both polymorphisms (rs4149117, rs7311358) were significantly associated with anemia. Significant associations were found between (rs2306283) and gastrointestinal disturbances and anemia. The GAAT haplotype was significantly more prevalent among good responders, while the TGGT haplotype was significantly associated with poor responders. These results highlight the importance of genetic testing in predicting MTX treatment outcomes and tailoring personalized treatment plans for patients with RA to improve efficacy and minimize adverse effects.
甲氨蝶呤（MTX）仍然是治疗类风湿性关节炎（RA）最常用的处方药。溶质载体有机阴离子转运体家族成员1B3（）和中的多态性可能在MTX药代动力学和患者预后中起关键作用。然而，沙特阿拉伯对这些多态性的研究仍然有限。我们评估了沙特RA患者中（rs4149117、rs7311358）和（rs2306283、rs4149056）多态性与MTX疗效和安全性的关联。这项多中心病例对照研究纳入了在吉达和塔伊夫被诊断为RA的患者。收集并分析了人口统计学和临床数据。使用桑格测序法对（rs4149117、rs7311358）和（rs2306283、rs4149056）多态性进行基因分型。进行了包括逻辑回归和单倍型分析在内的统计分析，以评估这些多态性、MTX疗效和毒性之间的关联。研究队列包括100名RA患者，其中46名对MTX反应良好，54名反应不佳。MTX反应不佳的患者中临床预测指标显著更高。两种多态性（rs4149117、rs7311358）均与贫血显著相关。在（rs2306283）与胃肠道紊乱和贫血之间发现了显著关联。GAAT单倍型在反应良好者中显著更常见，而TGGT单倍型与反应不佳者显著相关。这些结果凸显了基因检测在预测MTX治疗结果以及为RA患者制定个性化治疗方案以提高疗效和最小化不良反应方面的重要性。
