INFLUENCE OF C3435T POLYMORPHISM OF THE GENE MDR1 ON THE EFFICACY OF JUVENILE IDIOPATHIC ARTHRITIS THERAPY
https://doi.org/10.15690/pf.v10i5.822
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.
About the Authors
F. V. RokhlinaRussian Federation
assistant of the Vorontsov pediatrics department of the postgraduate and additional professional education faculty at the SPbSPMU
G. A. Novik
Russian Federation
N. M. Kalinina
Russian Federation
N. V. Bychkova
Russian Federation
Y. N. Filippova
Russian Federation
M. I. Zarayskiy
Russian Federation
References
1. Harris J. G., Kessler E. A., Verbsky J. W. Update on the Treatment of Juvenile Idiopathic Arthritis. Curr. Allergy Asthma Rep. 2013; 13: 337–346.
2. Bulatovic M., Heijstek M. W., Verkaaik M. et al. High Prevalence of Methotrexate Intolerance in Juvenile Idiopathic Arthritis. Art Rheumat. 2011; 63 (7): 2007–2013.
3. Chin J. E., Soffir R., Noonan K. E. et al. Structure and Expression of the Human MDR (P-Glycoprotein) Gene Family. Molecular and cellular biology. 1989. Р. 3808–3820.
4. Mironova Zh. A., Trofimov V. I., Simakova M. A. et al. Rossiiskii allergologicheskii zhurnal = Russian allergological journal. 2010; 3: 9–13.
5. Annese V., Valvano M. R., Palmieri O. et al. World Multidrug resistance 1 gene in inflammatory bowel disease: A Meta-analysis. J. Gastroenterol. 2006 June 21; 12 (23): 3636–3644.
6. Ambudkar S. V., Kimchi-Sarfaty C., Sauna Z. E. et al. P-glycoprotein: from genomics to mechanism. Oncogene. 2003; 22: 7468–7485.
7. Cantarini L., Simonini G., Frediani B. et al. Treatment strategies for childhood noninfectious chronic uveitis: an update. Expert. Opin. Investig Drugs. 2012; 21 (1).
8. Sauna Z. E., Kim I.-W., Ambudkar S.V.J Genomics and the mechanism of P-glycoprotein (ABCB1). Bioenerg Biomembr. 2007; 39: 481–487.
9. Pawlik A., Wrzesniewska J., Fiedorowicz-Fabrycy I. et al. The MDR1 3435 polymorphism in patients with rheumatoid arthritis. Int. J. Clin. Pharmacol Ther. 2004 Sep; 42 (9): 496–503.
10. Chen J., Chen L., Mao N. et al. Association of the MDR1 3435 polymorphism in patients with refractory rheumatoid arthritis in a Chinese population. Rheumatol. Int. 2011.
11. Cizmarikova M., Wagnerova M., Schonova L. et al. MDR1 (C3435T) polymorphism: relation to the risk of breast cancer and therapeutic outcome. The Pharmacogenomics Journal. 2010; 10: 62–69.
12. Sills G. J., Mohanraj R., Butler E. et al. Lack of Association between the C3435T Polymorphism in the Human Multidrug Resistance (MDR1) Gene and Response to Antiepileptic Drug Treatment. Epilepsia. 2005; 46 (5): 643–647.
13. Kato T., Hamada A., Mori S. et al. Genetic Polymorphisms in Metabolicand Cellular Transport Pathway of Methotrexate Impact Clinical Outcome of Methotrexate Monotherapy in Japanese patients with Rheumatoid Arthritis. Drug. Metab. Pharmacokinet. 2012; 27 (2): 192–199.
14. Jaap F., Stucki G., Piet L. C. M. van Riel. Rheumatoid Arthritis Measures Disease Activity Score (DAS), Disease Activity Score-28 (DAS28), Rapid Assessment of Disease Activity in Rheumatology (RADAR), and Rheumatoid Arthritis Disease Activity Index (RADAI). Arthritis & Rheumatism (Arthritis Care & Research). 2003 Oct. 15; 49 (5): S214–S224. Doi 10.1002/art.11407 © 2003, American College of Rheumatology.
15. Wallace C. A. Current management of juvenile idiopathic arthritis. Best Practice & Research Clinical Rheumatology. 2006. Р. 279–300.
16. Foeldvari I., Wierk A. Effectiveness of Leflunomide in Patients with Juvenile Idiopathic Arthritis in Clinical Practice. J. Rheumatol. 2010. pp. 1763–1767.
17. Ketlinskii S. A., Simbirtsev A. S. Tsitokiny [Cytokines]. St. Petersburg, «Izdatel'stvo Foliant» LLC, 2008. pp. 267–278.
Review
For citations:
Rokhlina F.V., Novik G.A., Kalinina N.M., Bychkova N.V., Filippova Y.N., Zarayskiy M.I. INFLUENCE OF C3435T POLYMORPHISM OF THE GENE MDR1 ON THE EFFICACY OF JUVENILE IDIOPATHIC ARTHRITIS THERAPY. Pediatric pharmacology. 2013;10(5):46-51. https://doi.org/10.15690/pf.v10i5.822