AB0156 A NOVEL ASSOCIATION OF TLR-2 (23 BPINS/DEL: RS111200466) POLYMORPHISM WITH ANKYLOSING SPONDYLITIS – A POSSIBLE ROLE IN DISEASE SUSCEPTIBILITY: A HOSPITAL BASED CASE-CONTROL STUDY
Authors: Abhisek Sabui, Rina Tripathy, Aditya Kumar Panda, Manoj Kumar Parida, Saumya Ranjan Tripathy, Bidyut Kumar Das
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Role of innate immunity in pathogenesis of ankylosing spondylitis (AS) has been well documented<sup>1</sup>. Higher expression of TLR2 has been reported in AS patients and associated with clinical severity<sup>2</sup>. Recently, a functional 23bp ins/del polymorphism at 5'UTR of TLR2 gene has been reported and association of variant with elevated TLR2 surface expression and proinflammatory molecules has been elegantly demonstrated<sup>3</sup>. This is associated with high TNF-alpha levels, one of the key molecules in the pathogenesis of AS <sup>4</sup>. In this preliminary study, we investigated the possible role of TLR2 (23bp ins/del) polymorphism with AS in a cohort from Odisha, India. <h3>Objectives:</h3> To investigate the role of TLR-2 (23 bp ins/del: rs111200466) Polymorphism in Ankylosing Spondylitis <h3>Methods:</h3> AS patients (n = 101), who fulfilled the ASAS classification criteria for axial spondyloarthritis or ASAS classification criteria for peripheral spondyloarthritis were enrolled along with 100 healthy age matched controls from similar geographical areas. Patients were examined in detail and BASDAI/BASFI recorded. TLR2 (23 bp ins/del) polymorphism was genotyped by polymerase chain reaction. Genotype and allele distribution among patients and controls were compared by Fisher's exact test. <h3>Results:</h3> All patients enrolled in the present study were males. The mean age of AS patients and healthy controls was 31.21±11.43 and 28.28±9.62 years, respectively. At the time of enrolment, mean disease duration of patients was 2.07±1.13 years. BASDAI and BASFI scores were above 5. Distribution of TLR2 (23 bp ins/del) polymorphism was in accordance with Hardy-Weinberg Equilibrium. Prevalence of del/del genotype was significantly higher in AS patients compared to healthy controls (P=0.01, OR=5.65), indicating a possible contributory role of TLR2 on predisposition to AS. Distribution of heterozygous genotype (ins/del) and minor allele (del) were comparable among different clinical categories. Furthermore, no significant association of TLR-2 polymorphism was observed with disease severity. <h3>Conclusion:</h3> TLR2 5'UTR homozygous mutants (23 bp deletion) were significantly associated with patients of AS in but not with disease severity. Larger sample size and levels of TNF alpha and IL17 in the mutants will further improve the understanding of its role in AS. <h3>References</h3> [1] Vanaki N, Aslani S, Jamshidi A, Mahmoudi M. Role of innate immune system in the pathogenesis of ankylosing spondylitis. Biomedicine &amp; Pharmacotherapy. 2018Sep30;105:130-43. [2] McCormack WJ, Parker AE, O'Neill LA. Toll-like receptors and NOD-like receptors in rheumatic diseases. Arthritis research &amp; therapy. 2009Oct;11(5):243. [3] Das B, Tripathy R, Pattanaik S, Panda A. 270 Association of tlr2 (23bp ins/del) polymorphism with systemic lupus erythematosus (sle) and p. falciparum malaria: a study in malaria endemic area of odisha, india. [4] Blandizzi C, Gionchetti P, Armuzzi AL, Caporali R, Chimenti S, Cimaz R, Cimino L, Lapadula G, Lionetti P, Marchesoni A, Marcellusi A. The role of tumour necrosis factor in the pathogenesis of immune-mediated diseases. International journal of immunopathology and pharmacology. 2014 Jan;27(1_suppl):1-0. <h3>Disclosure of Interests:</h3> None declared