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Pharmacogenetic Sex-Specific Effects of Methotrexate Response in Patients with Rheumatoid Arthritis

Methotrexate (MTX) is a commonly used drug for the treatment of rheumatoid arthritis (RA), but its effectiveness can vary greatly among patients. Pharmacogenetics, the study of how genetic variations can affect drug response, has the potential to improve the personalized treatment of RA by identifyi...

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Autores principales: Ceballos, Francisco C., Chamizo-Carmona, Eugenio, Mata-Martín, Carmen, Carrasco-Cubero, Carmen, Aznar-Sánchez, Juan J., Veroz-González, Raúl, Rojas-Herrera, Sara, Dorado, Pedro, LLerena, Adrián
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10300818/
https://www.ncbi.nlm.nih.gov/pubmed/37376109
http://dx.doi.org/10.3390/pharmaceutics15061661
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author Ceballos, Francisco C.
Chamizo-Carmona, Eugenio
Mata-Martín, Carmen
Carrasco-Cubero, Carmen
Aznar-Sánchez, Juan J.
Veroz-González, Raúl
Rojas-Herrera, Sara
Dorado, Pedro
LLerena, Adrián
author_facet Ceballos, Francisco C.
Chamizo-Carmona, Eugenio
Mata-Martín, Carmen
Carrasco-Cubero, Carmen
Aznar-Sánchez, Juan J.
Veroz-González, Raúl
Rojas-Herrera, Sara
Dorado, Pedro
LLerena, Adrián
author_sort Ceballos, Francisco C.
collection PubMed
description Methotrexate (MTX) is a commonly used drug for the treatment of rheumatoid arthritis (RA), but its effectiveness can vary greatly among patients. Pharmacogenetics, the study of how genetic variations can affect drug response, has the potential to improve the personalized treatment of RA by identifying genetic markers that can predict a patient’s response to MTX. However, the field of MTX pharmacogenetics is still in its early stages and there is a lack of consistency among studies. This study aimed to identify genetic markers associated with MTX efficacy and toxicity in a large sample of RA patients, and to investigate the role of clinical covariates and sex-specific effects. Our results have identified an association of ITPA rs1127354 and ABCB1 rs1045642 with response to MTX, polymorphisms of FPGS rs1544105, GGH rs1800909, and MTHFR genes with disease remission, GGH rs1800909 and MTHFR rs1801131 polymorphisms with all adverse events, and ADA rs244076 and MTHFR rs1801131 and rs1801133, However, clinical covariates were more important factors to consider when building predictive models. These findings highlight the potential of pharmacogenetics to improve personalized treatment of RA, but also emphasize the need for further research to fully understand the complex mechanisms involved.
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spelling pubmed-103008182023-06-29 Pharmacogenetic Sex-Specific Effects of Methotrexate Response in Patients with Rheumatoid Arthritis Ceballos, Francisco C. Chamizo-Carmona, Eugenio Mata-Martín, Carmen Carrasco-Cubero, Carmen Aznar-Sánchez, Juan J. Veroz-González, Raúl Rojas-Herrera, Sara Dorado, Pedro LLerena, Adrián Pharmaceutics Article Methotrexate (MTX) is a commonly used drug for the treatment of rheumatoid arthritis (RA), but its effectiveness can vary greatly among patients. Pharmacogenetics, the study of how genetic variations can affect drug response, has the potential to improve the personalized treatment of RA by identifying genetic markers that can predict a patient’s response to MTX. However, the field of MTX pharmacogenetics is still in its early stages and there is a lack of consistency among studies. This study aimed to identify genetic markers associated with MTX efficacy and toxicity in a large sample of RA patients, and to investigate the role of clinical covariates and sex-specific effects. Our results have identified an association of ITPA rs1127354 and ABCB1 rs1045642 with response to MTX, polymorphisms of FPGS rs1544105, GGH rs1800909, and MTHFR genes with disease remission, GGH rs1800909 and MTHFR rs1801131 polymorphisms with all adverse events, and ADA rs244076 and MTHFR rs1801131 and rs1801133, However, clinical covariates were more important factors to consider when building predictive models. These findings highlight the potential of pharmacogenetics to improve personalized treatment of RA, but also emphasize the need for further research to fully understand the complex mechanisms involved. MDPI 2023-06-05 /pmc/articles/PMC10300818/ /pubmed/37376109 http://dx.doi.org/10.3390/pharmaceutics15061661 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ceballos, Francisco C.
Chamizo-Carmona, Eugenio
Mata-Martín, Carmen
Carrasco-Cubero, Carmen
Aznar-Sánchez, Juan J.
Veroz-González, Raúl
Rojas-Herrera, Sara
Dorado, Pedro
LLerena, Adrián
Pharmacogenetic Sex-Specific Effects of Methotrexate Response in Patients with Rheumatoid Arthritis
title Pharmacogenetic Sex-Specific Effects of Methotrexate Response in Patients with Rheumatoid Arthritis
title_full Pharmacogenetic Sex-Specific Effects of Methotrexate Response in Patients with Rheumatoid Arthritis
title_fullStr Pharmacogenetic Sex-Specific Effects of Methotrexate Response in Patients with Rheumatoid Arthritis
title_full_unstemmed Pharmacogenetic Sex-Specific Effects of Methotrexate Response in Patients with Rheumatoid Arthritis
title_short Pharmacogenetic Sex-Specific Effects of Methotrexate Response in Patients with Rheumatoid Arthritis
title_sort pharmacogenetic sex-specific effects of methotrexate response in patients with rheumatoid arthritis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10300818/
https://www.ncbi.nlm.nih.gov/pubmed/37376109
http://dx.doi.org/10.3390/pharmaceutics15061661
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