{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T01:48:53Z","timestamp":1781920133087,"version":"3.54.5"},"reference-count":41,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,20]],"date-time":"2025-07-20T00:00:00Z","timestamp":1752969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institutional Fund Projects","award":["IFPIP: 561-247-1443"],"award-info":[{"award-number":["IFPIP: 561-247-1443"]}]},{"name":"Ministry of Education and King Abdulaziz University, Deanship of Scientific Research (DSR), Jeddah, Saudi Arabia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ph18071069","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T07:56:14Z","timestamp":1753084574000},"page":"1069","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Association of SLCO1B3 and SLCO1B1 Polymorphisms with Methotrexate Efficacy and Toxicity in Saudi Rheumatoid Arthritis Patients"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0886-4068","authenticated-orcid":false,"given":"Rania","family":"Magadmi","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahlam","family":"Alharthi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Alqurashi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibtisam","family":"Jali","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7136-566X","authenticated-orcid":false,"given":"Zeina","family":"Sharawi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha","family":"Jamal","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasser","family":"Bawazir","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0170-3747","authenticated-orcid":false,"given":"Mohammad","family":"Mustafa","sequence":"additional","affiliation":[{"name":"Rheumatology Unite, Department of Medicine, Faculty of Medicine, University of Jeddah, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami","family":"Bahlas","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basma","family":"Jamal","sequence":"additional","affiliation":[{"name":"King Fahad Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Daghasi","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Internal Medicine Department, Al Hada Armed Forces Hospital, Taif 26792, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman","family":"Altowairqi","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Internal Medicine Department, Al Hada Armed Forces Hospital, Taif 26792, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalal","family":"Al Shaer","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.36346\/sarjps.2024.v06i02.001","article-title":"A review of some the physiological effects of methotrexate on rheumatoid arthritis","volume":"6","author":"Hadi","year":"2024","journal-title":"South Asian Res. 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