Association of SLCO1B3 and SLCO1B1 Polymorphisms with Methotrexate Efficacy and Toxicity in Saudi Rheumatoid Arthritis Patients

<b>Background:</b> Methotrexate (MTX) remains the most commonly prescribed drug used to treat rheumatoid arthritis (RA). Polymorphisms in solute carrier organic anion transporter family member 1B3 (<i>SLCO1B3</i>) and <i>SLCO1B1</i> 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 <i>SLCO1B3</i> (rs4149117, rs7311358) and <i>SLCO1B1</i> (rs2306283, rs4149056) polymorphisms with MTX efficacy and safety in Saudi patients with RA. <b>Methods:</b> This multicenter, case-control study included patients diagnosed with RA in Jeddah and Taif. Demographic and clinical data were collected and analyzed. Genotyping of <i>SLCO1B3</i> (rs4149117, rs7311358) and <i>SLCO1B1</i> (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. <b>Results:</b> 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 <i>SLCO1B3</i> polymorphisms (rs4149117, rs7311358) were significantly associated with anemia. Significant associations were found between <i>SLCO1B1</i> (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. <b>Conclusions:</b> 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.