AB0001 ASSOCIATION OF MDR1 GENE G2677T POLYMORPHISM WITH METHOTREXATE RESISTANCE IN PATIENTS WITH UZBEK RHEUMATOID ARTHRITIS
Authors: Nargiza Abdurakhmanova, Khalmurad Akhmedov
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Methotrexate (MTX) is the most widely prescribed disease-modifying antirheumatic drug (DMARD) for treatment of rheumatoid arthritis (RA)[1]. According to different authors, in 25–40% [3] of cases "complete clinical remission" or "low disease activity" is not achieved, by reason of refractoriness to methotrexate and this may be related to the activity of the MDR1 (ABCB1) gene which is involved in its metabolism. According to many studies on the C3435T isoform MDR1 polymorphism CC genotype is associated with methotrexate refractoriness [2]. But a certain interest is also influenced by the other isoform of the MDR1 gene (G2677T) for the presence of resistance to methotrexate. <h3>Objectives:</h3> The aim of this research was to study the effect of MDR1 gene polymorphisms G2677T (rs2032582) on resistance to treatment with methotrexate in Uzbek patients with RA. <h3>Methods:</h3> The study involved 76 patients with RA of uzbek nationality and 24 healthy people. The average age of patients was 48,9 ± 15,9 years. RA was diagnosed according to the criteria of the American College of Rheumatology (ACR). 75.6% of patients had high and 24.4% moderate RA activity (DAS 28). All patients took methotrexate in monoterapy, at a dose of 7.5-15 mg for 3-6 months. All patients were genotyped by the MDR1 gene G2677T polymorphisms by using the polymerase chain reaction (PSR-Real time). <h3>Results:</h3> Genotyping of the G2677T isoform of MDR1 gene revealed the following results: in patients with CC genotype was found in 22 patients (28.9%), GT genotype was found in 31 patients (40.7%) and TT genotype was found in 23 patients (30.2%). In patients treated with methotrexate, the following disease activity was observed: in patients with CC genotype, the disease activity was Das28 &lt;2.6, with CT genotype Das28 3.2–4.5. Patients with the TT genotype had an activity of Das28&gt; 5.1. Despite the increase in the dose of methotrexate, the remission was not achieved. <h3>Conclusion:</h3> TT genotype G2677T isoform of MDR1 gene is associated with resistance to methotrexate. Patients with TT genotype are recommended to replace methotrexate with other DMARD preparations. Patients are recommended to conduct genotyping to the MDR1 gene for personal selection of drugs. <h3>References</h3> [1] Grabar P.B., Logar D. et al. (2008). Genetics determinants of methotrexate toxicity in rheumatoid artritis patients: a study of polymorphisms affecting methotrexate transport and folate metabolism. Eur J Clin Pharmacol. 64:1057-1068. [2] Pawlik A., Wrzesniewska J., Fiedorowicz-Fabrycy I. et al. The MDR1 3435 polymorphism in patients with rheumatoid arthritis. Int J Clin Pharmacol Ther. 2004Sep; 42 (9): 496-503. [3] Samara S.A., Irshaid Y.M. wt al. Association of MDR1 C3435T and RFC1 G80A polymorphisms with methotrexate toxicity and response in Jordanian rheumatoid arthritis patients. International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 - No. 9/2014 (746-755) <h3>Disclosure of Interests:</h3> None declared