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. 2025 Jul 20;18(7):1069.
doi: 10.3390/ph18071069.

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

Rania Magadmi  1 , Ahlam M Alharthi  1 , Lina A Alqurashi  2 , Ibtisam M Jali  3 , Zeina W Sharawi  2 , Maha H Jamal  1 , Yasser Bawazir  3 , Mohammad Mustafa  4 , Sami M Bahlas  3 , Basma T Jamal  5 , Hassan Daghasi  6 , Abdulrahman S Altowairqi  6 , Dalal Sameer Al Shaer  7
Affiliations

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

Rania Magadmi et al. Pharmaceuticals (Basel). .

Abstract

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

Keywords: methotrexate; personalized medicine; pharmacogenetics; polymorphism; rheumatoid arthritis; single nucleotide polymorphism.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Genotype distributions of SLCO1B3 polymorphisms (rs4149117 (A); and rs7311358 (B)) among African, American, Middle Eastern populations, and current Saudi cohort.
Figure 2
Figure 2
Genotype distributions of SLCO1B1 polymorphisms (rs2306283 (A); and rs4149056 (B)) among African, American, Middle Eastern populations, and current Saudi cohort.
Figure 3
Figure 3
Study flow chart of subjects’ enrollment and analysis.
See this image and copyright information in PMC

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