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Poster presentations: Clinical: Diagnosis and Outcome 2020

P124 Clock gene expression levels can differentially distinguish between ulcerative colitis and Crohn’s disease

Y. Weintraub1, S. Cohen1, N. Chapnik2, A. Yerushalmy-Feler1, A. Ben-Tov1, I. Dotan3, R. Tauman4, O. Froy2

1Sourasky Medical Center, Tel Aviv-Israel, Pediatric Gastroenterology, Tel Aviv, Israel, 2The Hebrew University, Institute of Biochemistry, Food Science and Nutrition, the Robert H Smith Faculty of Agriculture- Food and Environment, Rehovot, Israel, 3Rabin Medical Center, Division of Gastroenterology, Petah Tikva, Israel, 4Sourasky Medical Center, Tel Aviv-Israel, Sleep Disorders Center, Tel Aviv, Israel

Background

Pathophysiological mechanisms active in inflammatory bowel disease (IBD), such as mucosal barrier repair, innate and adaptive immune responses, intestinal motility and gut microbiome, all exhibit diurnal variations. Chronic disruption of the molecular clock augments inflammatory response. We have shown that newly diagnosed, naïve to treatment, young IBD patients showed reduced clock gene expression in both inflamed and non-inflamed intestinal tissues and in peripheral White blood cells (WBCs). This reduction correlated with disease activity1. Our aim in the current study was to determine whether certain clock genes correlate with disease activity scores or inflammatory markers in Crohn’s disease (CD) vs. ulcerative colitis (UC).

Methods

Fourteen CD and 11 UC patients, 8–22 years old, were recruited. Patients were evaluated upon diagnosis and during medical treatment. Disease activity scores, C-reactive protein (CRP) and faecal calprotectin (Fcal) levels were measured and WBC were analysed for clock gene (CLOCK, BMAL1, CRY1, CRY2, PER1 and PER2) expression. Clock gene expression levels were correlated to disease activity scores (clinically active vs. remission), CRP levels (<5 mg/l vs. >5 mg/l) and Fcal levels (<250 μg/mg vs. >250 μg/mg) in CD (21 samples) and UC patients (20 samples).

Results

In UC, CLOCK (p < 0.025), CRY1 (p < 0.033) and PER1 (p < 0.038) showed decreased expression when Fcal levels were >>250 μg/mg. When compared with the clinical status only BMAL1 showed reduced expression (p < 0.019). CRP levels showed no correlation with clock gene expression. In CD, CRP as well as the clinical status correlated with clock gene expression. Whereas CLOCK was reduced (p < 0.019), PER2 was induced (p < 0.005) when CRP levels were >5 mg/dl. Furthermore, CLOCK (p < 0.0005), PER1 (0.017) and PER2 (0.044) were reduced in CD patients with an active disease. However, Fcal did not correlate with clock gene expression.

Conclusion

Altered levels of certain clock genes were demonstrated in young CD and UC patients in relapse vs. remission and correlated with Fcal in UC patients and clinical status as well as CRP levels in CD patients.

Reference:

Weintraub Y et. al, Clin Gastroenterol Hepatol. 2019 Apr