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. 2025 Sep 12;18(9):1365.
doi: 10.3390/ph18091365.

Association of ABCG2 Polymorphisms with Methotrexate Efficacy and Toxicity in Saudi Rheumatoid Arthritis Patients

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

Association of ABCG2 Polymorphisms with Methotrexate Efficacy and Toxicity in Saudi Rheumatoid Arthritis Patients

Zeina W Sharawi et al. Pharmaceuticals (Basel). .

Abstract

Background/Objectives: Methotrexate (MTX) is currently the most widely used treatment for Rheumatoid Arthritis (RA) due to its demonstrated efficacy and well-known safety profile. However, the effectiveness and toxicity of MTX can vary among patients, partly due to genetic factors. Therefore, this study aimed to investigate the associations between the polymorphisms in the ABC subfamily G member 2 (ABCG2) gene and MTX effectiveness/toxicity in Saudi Arabia RA patients. Methods: The study is a retrospective, multicenter, case-control study that uses Sanger sequencing techniques for genotyping. Results: More than half of the patients (55.56%) were poor responders, with a slightly higher mean age. However, there was no significant difference between the two groups, not only in terms of age but also in other demographics and clinical factors. Regarding the rs2231137 polymorphism, the CC, CT, and TT genotype frequency were 91%, 7%, and 2%, respectively. The mutated variant (TT) was only observed in the positive rheumatoid factor group. Notably, none of these genotypes displayed any significant correlation with demographic characteristics, clinical features, or MTX efficacy/toxicity. Conclusions: This study is the first pharmacogenetic study of rs2231137 polymorphism in RA patients utilizing linear regression, revealing that rs2231137 polymorphism is not a predictor of either MTX efficacy or toxicity in RA patients. Therefore, more research is needed.

Keywords: ABCG2; methotrexate; pharmacogenetics; 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.

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