AB1144 Influence the level of PGP activity (product of MDR1GENE) on the efficiency of basic therapy in children with juvenile idiopathic arthritis

• Published in: Annals of the rheumatic diseases Vol. 71; no. Suppl 3; p. 703
• Main Authors: Rokhlina, F., Dubko, M., Bychkova, N., Kalinina, N., Zaraiski, M., Novik, G.
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and European League Against Rheumatism 01.06.2013; BMJ Publishing Group LTD
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2012-eular.1142

Background Studies of the MDR1 gene started from the early 80s of the XX century, when first studied protein expression Pgp-170. In 2000, for the first time it was found that the “silent” variant C3435T in exon 26 of MDR1 gene is associated with expression levels of Pgp-170, the study was conducted among Europeans with gastrointestinal diseases [S. Hoffmeyer and authors]. It is known that in carriers of genotype TT (the gene MDR1) observed a fourfold decrease in activity of Pgp-170, and allele carrier 3435C MDR1 gene is associated with elevated activity of Pgp-170, which in turn leads to insufficient anti-inflammatory effect of cytostatic therapy. [Pawlik A. and authors]. Objectives The aim of our study is to detect the influence of C3435T polymorphism (gene MDR1) and the expression level of Pgp on the efficiency of cytostatic therapy in children with juvenile idiopathic arthritis. Results We examined 50 children with various forms of JIA (oligoarthritis - 10 children (20%), polyarthritis - 17 children (34%), systemic arthritis - 10 children (20%), psoriatic arthritis - 1 child (2%), enthesitis and enthesitis-related arthritis - 12 children (24%)). All of the children received methotrexate as a basic therapy (intramuscularly at a dose of 15 mg/m2/week). CC genotype (allele 3435C) is defined in 16% of children (oligoarthritis – 1 child, polyarthritis - 4 children, systemic arthritis - 2 children and enthesitis and enthesitis-related arthritis – 1 child). TT genotype (allele 3435T) occurs in 30% of the children (oligoarthritis – 1 child, polyarthritis - 7 children, systemic arthritis – 4 children and enthesitis and enthesitis-related arthritis – 3 children. The most common genotype CT is determined by more than half the children (54%) - oligoarthritis - 8 patients, polyarthritis - 6 children, systemic arthritis - 4 children, psoriatic arthritis – 1 child, enthesitis and enthesitis-related arthritis – 8 patients Conclusions According to international studies is not responsible for the classic basic therapy are about 30%. In the study, we found that 75% of JIA patients with genotype CC, required prescribing of a biologically active therapy, due to the inefficiency of basic therapy. Whereas only 46.6% of patients with genotype TT required prescribing of biologically active drugs, which by assumption is associated with the level of Pgp-170. Only 25.9% of patients with genotype CT were in need of additional therapy with biologically active agents. References Pawlik A., Wrzesniewska J., Fiedorowicz-Fabrycy I., Gawronska-Szklarz B., The MDR1 3435 polymorphism in patients with rheumatoid arthritis.Int.J.Clin.Pharmacol.Ther.2004, v, 42 (9) p.496-503 S. Hoffmeyer, O. Burk, O. von Richter et al. Functional polymorphisms of the human multidrugresistance gene: Multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo.Proc.Natl.Acad.Sci.USA. 2000, v.97, p.3473-3478. Disclosure of Interest None Declared