Circadian clock gene disruption in white blood cells of patients with celiac disease

Y. Weintraub, S. Cohen, A. Yerushalmy-Feler, N. Chapnik, S. Tsameret, A. Anafy, E. Damari, A. Ben-Tov, R. Shamir, O. Froy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Clock gene disruption has been reported in inflammatory and autoimmune diseases. Specifically, it has been shown that clock gene expression is down-regulated in intestinal tissue and peripheral blood mononuclear cells of patients with inflammatory bowel disease (IBD). We aimed to determine the systemic expression of the circadian clock genes in newly diagnosed untreated, young patients with celiac disease (CeD). We prospectively enrolled patients younger than 20 years old who underwent diagnostic endoscopic procedures either for CeD diagnosis or due to other gastrointestinal complaints, at the pediatric and adult gastroenterology units, the Tel Aviv Sourasky Medical Center from 8/2016–8/2022. Demographic data, anthropometric parameters, and endoscopic macroscopic and microscopic findings were obtained. Blood samples were obtained to determine tissue transglutaminase (tTG) and core clock gene (CLOCK, BMAL1, PER1, PER2, CRY1, CRY2) expression in white blood cells (WBC). Thirty individuals were analyzed (18 with newly diagnosed CeD and 12 controls). Expression of the clock genes CLOCK, BMAL1, CRY2, PER1 and PER2 was significantly reduced in CeD patients compared to controls, while CRY1 did not differ between the groups. In conclusion, newly diagnosed, untreated, young patients with CeD have reduced clock gene expression in WBC compared to controls. These results suggest that, in CeD, the inflammatory response is associated with systemic disruption of clock gene expression, as is manifested in other inflammatory and autoimmune diseases. ClinicalTrials.gov identifier: NCT03662646.

Original languageAmerican English
JournalBiochimie
DOIs
StateAccepted/In press - 2023

Bibliographical note

Funding Information:
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Financial support from the Hebrew University allowed this work to be performed.

Publisher Copyright:
© 2023 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM)

Keywords

  • Celiac disease
  • Circadian rhythms
  • Clock
  • Gene expression
  • Tissue transglutaminase

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