Genomics, genetic basis of disease and antigen presentation AB0001 ASSOCIATION OF MDR1 GENE G2677T POLYMORPHISM WITH METHOTREXATE RESISTANCE IN PATIENTS WITH UZBEK RHEUMATOID ARTHRITIS Nargiza Abdurakhmanova 1 , Khalmurad Akhmedov 2 . 1 Tashkent Medical Academy, Tashkent, Uzbekistan; 2 Tashkent Medical academy, Tashkent, Uzbekistan Background: Methotrexate (MTX) is the most widely prescribed disease-modify- ing antirheumatic drug (DMARD) for treatment of rheumatoid arthritis (RA)[1]. According to different authors, in 25–40% [3] of cases “complete clinical remis- sion” 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 iso- form MDR1 polymorphism CC genotype is associated with methotrexate refracto- riness [2]. But a certain interest is also influenced by the other isoform of the MDR1 gene (G2677T) for the presence of resistance to methotrexate. Objectives: The aim of this research was to study the effect of MDR1 gene poly- morphisms G2677T (rs2032582) on resistance to treatment with methotrexate in Uzbek patients with RA. Methods: 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 diag- nosed 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). Results: 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 geno- type 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 <2.6, with CT genotype Das28 3.2–4.5. Patients with the TT genotype had an activity of Das28> 5.1. Despite the increase in the dose of methotrexate, the remission was not achieved. Conclusion: 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 recom- mended to conduct genotyping to the MDR1 gene for personal selection of drugs. REFERENCES [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 Pharma- col Ther. 2004 Sep; 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 Clini- cal Pharmacology and Therapeutics, Vol. 52 - No. 9/2014 (746-755) Disclosure of Interests: None declared DOI: 10.1136/annrheumdis-2019-eular.5815 AB0002 INCREASED SENSITIVITY TO DNA DAMAGING AGENTS IN HUMAN PERIPHERAL BLOOD MONONUCLEAR CELLS FROM PATIENTS WITH RHEUMATOID ARTHRITIS Olga Brzezińska 1 , Grzegorz Galita 2 , Anna Macieja 2 , Anna Lewandowska-Polak 1 , Joanna Sarnik 1 , Tomasz Popławski 2 , Joanna Makowska 1 . 1 Medical University of Lodz, Department of Rheumatology, Łódź, Poland; 2 University of Lodz, Department of Molecular Genetics, Łódź, Poland Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder with not fully elucidate pathogenesis. Rheumatoid arthritis patients have increased risk of developing lymphomas. One of the possible mechanisms of this predisposition is increased genomic instability and impaired DNA repair. It is unclear how this genomic instability contributes to diseases pathogenesis. Objectives: The aim of this study was to analyze the sensitivity and repair effi- ciency of mononuclear cells isolated from RA patients to DNA damaging agents. Methods: The study group consisted of 22 patients with RA (age years - 60,77±13,00 women-17, men - 5) hospitalized in the Department of Rheumatology between 2017 and 2018 and 10 healthy controls without autoimmune and oncological diseases in clinical history (age 44,09±16,56; women-5, men-6). The peripheral blood mononuclear cells (PBMC) from all subjects were isolated. Using comet assay the degree of intracellular DNA damage as a result of exposure to standard damage factors: tert- butyl hydroperoxide (TBH), bleomycin, methyl methanesulfonate (MMS) and UV radiation was assessed. Results: RA patients show a statistically significant higher level of endog- enous damage in PBMC DNA than controls (mean RA- 8,64% vs 4,68% in control; p<0,001). The extent of the DNA damage induced by TBH, MMS as well as UV was significantly higher in PBMC derived from RA patients than in healthy counterparts (p<0,001). The DNA of RA patients treated with TBH was repaired less effectively than in control (p<0,0001). Significantly higher percentage of DNA damage in RA DNA (p<0,0001) under the influence of bleomycin and clearly marked repair processes were observed. Among the healthy controls lower percentage of DNA was damaged, and although the repair process was slower but the final percent of DNA damage was lower than in RA cases (p<0,0001). Conclusion: DNA of people with rheumatoid arthritis is significantly more sus- ceptible to damage in baseline and induced. The kinetics of DNA repair from RA patients after the introduction (TBH and bleomycin) was statistically less effective as compared to healthy control. Understanding the ethology of this phenomenon in RA may provide insight into disease pathogenesis and explain the increased susceptibility of patients to malignancies. Acknowledgement: The project is financed under the funds of the National Sci- ence Center (2017/25/B/NZ6/01358) Disclosure of Interests: None declared DOI: 10.1136/annrheumdis-2019-eular.6155 AB0003 GENETICS OF PAIN IN WOMEN WITH FIBROMYALGIA: THE PROMISING ROLE OF REDUCING SEDENTARY BEHAVIOUR Fernando Estevez-Lopez 1,2 , Diego Salazar-Tortosa 1 , Virginia A. Aparicio 1 , Daniel Camiletti-Moirón 3 , Blanca Gavilán Carrera 1 , Pedro Acosta-Manzano 1 , Inmaculada C. Alvarez-Gallardo 1 , Víctor Segura-Jiménez 3 , Alberto Soriano Maldonado 4 , Patrick Finan 5 , Rinie Geenen 6 , Manuel Delgado-Fernández 1 , Luis J. Martínez-González 7 , Jonatan R. Ruiz 1 , María J. Álvarez-Cubero 1,7 . 1 University of Granada, Granada, Spain; 2 Ulster University, Belfast, United Kingdom; 3 University of Cádiz, Cádiz, Spain; 4 University of Almería, Almería, Spain; 5 John Hopkins University, Baltimore, United States of America; 6 Utrecht University, Utrecht, Netherlands; 7 GENyO (Pfizer-University of Granada- Andalusian Government Centre for Genomics and Oncological Research), Granada, Spain Background: Fibromyalgia is characterised by chronic pain and a heterogene- ous presentation of other symptoms (e.g., fatigue and depression) [1]. It is widely accepted that pain is promoted by both genetic susceptibility and environmental factors such as people’s behaviours [2]. In addition to genotype individual associ- ations and gene-gene interactions, when considering complex phenotypes such as pain, gene-environmental interactions are likely present and can help to better understand the disease (i.e. by unravelling underlying mechanisms [3]). Objectives: To test the individual association of 64 polymorphisms (34 candi- date-genes) and the gene-gene, gene-physical activity, and gene-sedentary behaviour interactions with pain and pain-related cognitions in fibromyalgia. Methods: In 274 women with fibromyalgia, saliva samples were collected for extracting DNA. We measured physical activity and sedentary behaviour by accelerometers for a week, pain with algometry and questionnaires, and pain cog- nitions with questionnaires. Age, body fat, and analgesics and antidepressants consumption were included as covariates. Significance was set at P-values lower than the Bonferroni’s correction or P- and false discovery rate values lower than 0.05. Results: The rs6311 and rs6313 polymorphisms were individually related to algo- meter scores. The interaction of rs4818 and rs1799971 polymorphisms was related to pain catastrophizing. Five gene-behaviour interactions were significant: the interactions of sedentary behaviour with rs1383914, rs6860, rs4680, rs165599, and rs12994338 polymorphisms were associated with the bodily pain subscale of the SF-36. Conclusion: The HTR2A gene (individually), COMT and OPRM1 gene-gene interaction, and the interactions of sedentary behaviour with ADRA1A, CHMP1A, COMT, and SCN9A genes were associated with pain-related outcomes in fibro- myalgia females. Besides indicating the relevance of genetic background for pain and pain-catastrophizing, the observed genotype-behaviour interactions suggest that the effects of sedentary behaviour on pain may depend on the genotype of women with fibromyalgia. Future clinical experimental research should examine whether reducing sedentary behaviour is particularly beneficial for reducing pain in women with specific genotypes. 1468 Scientific Abstracts on March 22, 2022 by guest. 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