RESUMEN
OBJECTIVE: To study the expression, function and polymorphism of MDR-1 protein on the peripheral blood lymphocytes in patients with RA following treatment with MTX and its relationship with response to therapy. METHODS: RA patients naïve to MTX/DMARD- and glucocorticoid were enrolled. Expression and function of MDR-1 was carried out by flow cytometry at baseline and after 4 months of therapy. MDR-1 expression was measured by relative fluorescence intensities and percentage of positive cells. MDR-1 function was assessed by Rhodamine efflux in presence or absence of verapamil. Patients with reduction in disease activity score 28 ≥1.2 were defined as responders and <1.2 as non-responders. Three single nucleotide polymorphisms in MDR-1 gene, 3435T, 1236T and 2677T/A were studied. RESULTS: Fifty-two patients of RA were grouped into responders (n = 41), and non-responders (n = 11) as per the defined criteria. There was no difference between the groups in terms of age, sex ratio or duration of illness, MTX dose and follow-up duration. The expression and function of the MDR-1 protein reduced significantly in the responder group after the treatment with MTX when compared to the baseline evaluation. The decrease was significant when compared to the non-responders at the fourth month. MDR-1 expression and function either increased or remained the same in the non-responder group after treatment with MTX. MTX unresponsiveness was not related to any of the three polymorphisms studied. CONCLUSION: Persistent expression and function of MDR-1 identifies a subset of RA patients not responding to MTX. Its early recognition may help in appropriately modulating therapy.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Metotrexato/uso terapéutico , Polimorfismo de Nucleótido Simple , Adulto , Artritis Reumatoide/metabolismo , Femenino , Técnicas de Genotipaje , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Insuficiencia del TratamientoRESUMEN
CONTEXT: Indians are at high risk of developing type 2 diabetes mellitus (T2DM) at an early age, despite their lower body mass index. Studies on the etiology of patients presenting as early-onset T2DM in this racial group are not available. OBJECTIVE: The objective was to delineate the clinical features in young Indian patients with T2DM and to determine the role of mutations in the hepatocyte nuclear factor 1alpha (HNF1alpha) gene [MODY3 (maturity-onset diabetes of the young, type 3)], mitochondrial A3243G mutation, and islet autoimmunity in its etiology. DESIGN: This was an observational cohort study. SETTING: The setting was an outpatient diabetes clinic in a teaching hospital. PATIENTS: Ninety-six consecutive young patients with T2DM (onset, Asunto(s)
Enfermedades Autoinmunes
, Diabetes Mellitus Tipo 2
, Genes Mitocondriales/genética
, Factor Nuclear 1-alfa del Hepatocito/genética
, Islotes Pancreáticos/inmunología
, Adulto
, Edad de Inicio
, Autoanticuerpos/inmunología
, Enfermedades Autoinmunes/etiología
, Enfermedades Autoinmunes/genética
, Enfermedades Autoinmunes/inmunología
, Estudios de Cohortes
, Diabetes Mellitus Tipo 2/etiología
, Diabetes Mellitus Tipo 2/genética
, Diabetes Mellitus Tipo 2/inmunología
, Salud de la Familia
, Femenino
, Genotipo
, Humanos
, India
, Masculino
, Linaje
, Mutación Puntual
, Polimorfismo Genético