INFLUENCE OF C3435T POLYMORPHISM OF THE GENE MDR1 ON THE EFFICACY OF JUVENILE IDIOPATHIC ARTHRITIS THERAPY

Abstract

Juvenile idiopathic arthritis (JIA) is a multifactorial disease: its pathogenesis includes immunological and genetic factors. Gene MDR1 is responsible for resistance to various cytotoxic drugs. Product of gene MDR1 - P-glycoprotein (P-gp) acts as a transmembrane pump, thus affecting action of drugs. The research objective was to determine connection of C3435T polymorphism of gene MDR1 with P-protein’s expression level in children with JIA. P-protein was revealed in all the patents involved in our trial: the protein was revealed on peripheral blood lymphocytes before and after stimulation of interleukin 2. The authors also picked out genome DNA using phenol-chloroform extraction and detected C3435T polymorphism of the gene MDR1 using polymerase chain reaction. Methotrexate concentration in blood serum was determined using a standard method of fluorescent polarization (FPIA) using the Abbott apparatus TDxFLx. Statistical manipulation of the data obtained in the course of the trial was conducted using software Statistica 6.0. C3435T polymorphism of gene MDR1 affects therapy efficacy. Determination of both basal and stimulated (in vitro) P-glycoprotein may be used as additional criterion in the evaluation of disease activity.

Keywords

• juvenile idiopathic arthritis
• p-glycoprotein
• multidrug resistance gen
• c3435t polymorphism