SAT0413 Genetic Aspect of Inter-Individual Variability in The Response To Non-Steroidal anti-inflammatory Drugs in Axial Spondyloarthritis:
Authors: G. Kilic, C. Sakalar, B. Kurt, M. Cakir, E. Kilic, S. Ozgocmen
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Non-steroidal anti-inflammatory drugs (NSAIDs) are first line therapies in patients with axial spondyloarthritis (axSpA). Patients with axSpA frequently response to NSAIDs and good response to NSAIDs is an important clinical feature. However, nearly 20–50% of patients with ankylosing spondylitis may have active disease despite NSAID treatment. NSAIDs acts through cyclooxygenase (COX) inhibition and inter-individual variability in response to NSAIDs may be related to genetic factors that regulate COX enzymes. <h3>Objectives</h3> We hypothesized that incomplete inhibition of COX enzymes as a consequence of genetic variability in the regulatory region of the COX genes may influence the response to NSAIDs. To examine this hypothesis, we investigated the association between selected polymorphism in COX-1 and COX-2 genes and NSAIDs response in axSpA. <h3>Methods</h3> Patients with axSpA who were followed by our outpatient clinic and met ASAS classification criteria for axSpA were enrolled. Healthy controls were recruited from hospital staff and visitors. Patients and controls were assessed for clinical and laboratory data. Inadequate response (IR) to NSAID therapy was defined either as persistence of symptoms despite maximal dosage of NSAIDs therapy or as persistent disease activity with a BASDAI&gt;4 or an ASDAS &gt;2 during NSAID therapy. Promoter variant of COX-2 -765G&gt;C that is located in a putative binding site for the Sp1 transcription factors plays significant role as a positive activator of COX2 transcription. The Pro17Leu variant of COX-1–50C/T is associated with changed prostaglandin production and coxib selectivity. The DNA was isolated from blood samples the frequency of both COX-2- 765G/C (rs20417) and COX-1–50C/T (rs3842787) polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods using the Faul restriction enzyme and appropriate primers. <h3>Results</h3> A total of 177 patients with axSpA (108M, 69F; mean age, 37.5±9.6 yrs) and 103 healthy controls (60M, 43F; mean age, 33.0±7.6 yrs) were included. Genotype distribution is given in the table. We did not found any significant differences in genotype of COX polymorphism regarding good/inadequate response to NSAIDs in patients with axSpA. Also there was no significant difference in the allele frequency distributions of COX-2–765G/C and COX-1–50C/T between patients and healthy controls. <h3>Conclusions</h3> The current study is the first to investigate the possible role of genetic variation of COX genes in the NSAID response in axSpA. Our results suggest that genetic polymorphism of COX-1–50C/T and COX-2 -765 do not play a significant role in NSAID response in axSpA. Further studies are needed to confirm these finding in patients with axSpA from different ethnic population. <h3>Acknowledgement</h3> Many thanks to Erciyes University Scientific Research Project Department who supported our project (TTU-2013–4882) <h3>Disclosure of Interest</h3> None declared