P080 Mucosal clock and inflammation regulatory genes are disrupted in treatment naïve pediatric patients with ulcerative colitis

Abstract Background The human circadian clock is present in cells throughout the body. It consists of CLOCK and BMAL1 that heterodimerize bind to E-box sequences mediate transcription a large number genes, including Periods (PERs) Cryptochromes (CRYs). PERs CRYs constitute part negative feedback loop inhibit CLOCK:BMAL1-mediated transcription. Recently, we have shown patients with active ulcerative colitis (UC) display tissue-specific misalignment molecular reverts normal following effective treatment. Several genes also function as anti-inflammatory regulators. RORa, PPARa PPARg are positive regulators mechanism induce expression IkB, suppressor NFkB. In same manner, PCG1a induces IL10. Our aim was characterize these compared core determine their correlation UC patients. Methods Clock gene patterns using whole transcriptome RNA sequencing were retrieved from IBD Transcriptome Metatranscriptome Meta-Analysis platform (TaMMA IBD). We rectal biopsy 12 isoforms (AMPK, BMAL1, CLOCK, CRY1, CRY2, PER1, PER2, PCG1a, PPARa, PPARg, REV-ERB, RORg SIRT1) 206 treatment naïve pediatric (age 12.9±3.2; 54% male) 20 healthy controls 13.9±3.3; 45% male). Spearman correlations calculated between all within each control cohorts. Results Core genes: BMAL (p<0.0001), (p<0.01) CRY1 regulator RORa (p<0.0001) upregulated controls. contrast, other regulatory (p<0.01), decreased. levels show discordant For example, BMAL/REV-ERBa well PPARg/REV-ERBa inverted (r=-0.44 vs. r=0.13 r =-0.4 r=0.3, respectively). Figure 1. Expression inflammation Conclusion disrupted, decreased demonstration some highlights disruption inflammation. Since ameliorate inflammation, reduced may explain not only dysregulation but increased tissue