Genetic Polymorphisms of GGH and ABCC2 Are Associated with Methotrexate Intolerance in Patients with Rheumatoid Arthritis
| Autor: | Jerusalem Calvo-Gutiérrez, Natalia Mena-Vázquez, Rafael Cáliz-Cáliz, Barbara Manzanares-Martin, Blanca Panero-Lamothe, Rafaela Ortega-Castro, Clementina López-Medina, Mayte Ruiz-Jiménez, Eduardo Collantes-Estevez, Pilar Font-Ugalde, Alejandro Escudero-Contreras, Alberto Jiménez-Morales |
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| Přispěvatelé: | [Escudero-Contreras,A, López-Medina,C, Collantes-Estévez,E, Ortega-Castro,R, Calvo-Gutiérrez,J, Font-Ugalde,P] Rheumatology Department, Reina Sofia University Hospital, Cordoba, Spain. [Escudero-Contreras,A, Manzanares-Martín,B, Font-Ugalde,P] Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain. [Escudero-Contreras,A, Font-Ugalde,P] Medical and Surgical Sciences Department, University of Cordoba, Cordoba, Spain. [Mena-Vázquez,N, Panero-Lamothe,B] Institute of Biomedical Research from Malaga (IBIMA), Malaga, Spain. [Mena-Vázquez,N, Panero-Lamothe,B] Rheumatology Department, Regional University Hospital from Malaga, Malaga, Spain. [Manzanares-Martín,B] Immunology and Allergology Department, Reina Sofia University Hospital, Cordoba, Spain. [Cáliz-Cáliz,R] Rheumatology Department, Virgen de las Nieves University Hospital, Granada, Spain. [Jiménez-Morales,A] Pharmacy Department, Virgen de las Nieves University Hospital, Granada, Spain. [Ruiz-Jiménez,M] Medical Science Liaison Roche, Roche Farma, Madrid, Spain., This study was funded by an unrestricted grant from Roche Pharma and supported by 'Red Andaluza para la Investigación de Enfermedades Reumáticas (RAIER)'. |
| Rok vydání: | 2021 |
| Předmět: |
rheumatoid arthritis
musculoskeletal diseases medicine.medical_specialty Genotype Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective Studies [Medical Subject Headings] Chemicals and Drugs::Nucleic Acids Nucleotides and Nucleosides::Nucleotides [Medical Subject Headings] Polimorfismo genético Single-nucleotide polymorphism Artritis reumatoide Genetic polymorphisms Gastroenterology Metotrexato Article methotrexate Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] Polymorphism (computer science) Internal medicine medicine genetics Adverse effect Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings] Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism Genetic::Polymorphism Single Nucleotide [Medical Subject Headings] business.industry biomarkers Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds 2-Ring::Pteridines::Pterins::Aminopterin::Methotrexate [Medical Subject Headings] General Medicine medicine.disease Genética Diseases::Musculoskeletal Diseases::Rheumatic Diseases::Arthritis Rheumatoid [Medical Subject Headings] Biomarcadores Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Evaluation Studies as Topic::Clinical Trials as Topic::Multicenter Studies as Topic [Medical Subject Headings] Rheumatoid arthritis Cohort Toxicity Medicine Methotrexate Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings] business Genotipo medicine.drug |
| Zdroj: | Journal of Clinical Medicine, Vol 10, Iss 4070, p 4070 (2021) Journal of Clinical Medicine Volume 10 Issue 18 |
| ISSN: | 2077-0383 |
| Popis: | Objective: to identify new single-nucleotide polymorphisms (SNPs) in genes encoding proteins involved in methotrexate (MTX) metabolism and to evaluate the associations of these SNPs with MTX toxicity or intolerance in a southern Spanish cohort of patients with rheumatoid arthritis (RA). Methods: An observational, retrospective, and multicenter study was conducted at three participating hospitals in southern Spain. The main variable was intolerance to MTX (i.e., bDMARD monotherapy), defined as an interruption of treatment due to adverse events or toxicity. Patients being treated with MTX and bDMARDs (combined treatment) at the time of the study visit were considered “tolerant” of MTX. Ten polymorphisms were selected for sequencing in our patients according to a literature review. Each polymorphism was classified according to three possible genotypes (e.g., two homozygous (AA or GG) and one heterozygous (AG)), and the association of these combinations with MTX intolerance was evaluated. Results: A total of 227 patients were included in the final analysis (107 intolerant of MTX and 120 tolerant). A significant association was observed between MTX intolerance and the GGH-T401C AA/AG genotype (OR 2.13, 95% CI 1.06–4.29) in comparison with the GG genotype. On the other hand, an inverse association was observed between the ABCC2-C24T TT/TC genotype and intolerance to MTX (OR 0.59, 95% CI 0.35–1.00) in comparison with the CC genotype. Conclusion: This study provides new data on the association between genetic polymorphisms and MTX intolerance, which may contribute to the development of new biomarkers and personalized medicine in patients with RA. |
| Databáze: | OpenAIRE |
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