POS0031 FUNCTIONAL GENOMICS INVESTIGATION OF THE ANKYLOSING SPONDYLITIS ASSOCIATED LOCUS RUNX3

Background Ankylosing Spondylitis (AS), is a highly heritable disease with >100 genomic loci incriminated. Among these, RUNX3, transcription factor (TF) involved in diverse immunological processes, robustly (10 −15 ) associated. [ 1] We have extensively investigated the single nucleotide polymorphism (SNP) rs4648889 located 2kb regulatory locus upstream of RUNX3 promoter. demonstrated that association between AS and this SNP can be explained by allele-specific effects on TF recruitment (including IRF4, IRF5 NuRD complex) alter gene expression, specifically CD8+ T-cells, having crucial role T-cells function. [2, 3] Further, we recently shown clear chromatin looping event region encompassing promoter confirming functional genetic variant. 4] Objectives The purpose work is: (1) to better characterise landscape whole AS-associated (2) determine single-cell expression -related genes identified previously 2, lymphocytes. Methods Chromosome conformation capture (3C) technique followed qPCR was performed define events at relevant cell lines, including Jurkat U937 monocytes-like cells. 10X Chromium (sc) sequencing profile T cells obtained from cases. Results In addition recent results published, 3C-qPCR experiments revealed high interaction frequency distal an intronic (called Int2), overlapping open binding sites. This reproducible both lines analysed. Four different clusters were peripheral blood via 10x sc-seq based RUNX3. Five other ( TBX21 , EOMES CHD4 IKZF3 [2] considered: cluster 1 showed strong co-expression for IKZF3, EOMES. Further analysis required characterize subpopulation. Conclusion has plausible AS, probably regulating DNA looping. These observations are critically important defining dysregulated pathways potential therapeutic drug targets. References [1]IGAS et al. Nat Genet . 2013 Jul;45(7):730-8. [2]Vecellio M. al, Ann Rheum Dis. 2016 Aug;75(8):1534-40. [3]Vecellio Arthritis Rheumatol 2020. doi: 10.1002/art.41628. [4]Cohen CJ. Front 2022 doi.org/10.3389/fgene.2021.741867. Disclosure Interests Carla Cohen: None declared, Davide Simone: Carlo Selmi Speakers bureau: fee (AbbVie, Amgen, Alfa-Wassermann, Biogen, Celgene, Eli-Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, Sanofi-Genzyme), Consultant of: Consulting Grant/research support from: Research Pfizer), aul Bowness Regeneron, Celgene/BMS GSK, Paul Bryan Wordsworth: Matteo Vecellio: declared