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Pharmacogenomics ; 15(6): 807-20, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24350725

RESUMEN

AIM: The aim of our study was to characterize the association of clinicopathological variables and the SLC19A1/RFC-1 G80A polymorphism in methotrexate (MTX)-related toxicity in Portuguese patients with rheumatoid arthritis. PATIENTS & METHODS: The study included 233 consecutively recruited patients with rheumatoid arthritis under MTX treatment. The SLC19A1 G80A polymorphism was evaluated by PCR-RFLP. RESULTS: Statistical analysis revealed that SLC19A1 80G carriers had increased risk of gastrointestinal toxicity (odds ratio [OR]: 2.61, p = 0.019) and that regular folic acid supplementation was associated with both overall and gastrointestinal toxicity protection (OR: 0.15, p < 0.001 and OR: 0.19, p < 0.001, respectively). Multivariate analysis confirmed the association of SLC19A1 80G and regular folic acid supplementation to gastrointestinal toxicity (OR: 5.53 and 0.13, respectively). Moreover, a multivariate Cox regression model demonstrated a higher risk of earlier gastrointestinal toxicity in SLC19A1 80G carriers (hazard ratio: 3.63, p = 0.002). CONCLUSION: SLC19A1 G80A genotyping may be a useful tool for clinicians to identify patients at higher risk for developing gastrointestinal toxicity related to MTX treatment.


Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Biomarcadores/metabolismo , Tracto Gastrointestinal/efectos de los fármacos , Metotrexato/efectos adversos , Metotrexato/uso terapéutico , Proteína Portadora de Folato Reducido/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Antirreumáticos/efectos adversos , Antirreumáticos/uso terapéutico , Femenino , Ácido Fólico/administración & dosificación , Tracto Gastrointestinal/metabolismo , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Portugal , Estudios Retrospectivos
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