Methylation of RUNX3 Promoter 2 in the Whole Blood of Children with Ulcerative Colitis

Genes (Basel). 2022 Sep 1;13(9):1568. doi: 10.3390/genes13091568.

Abstract

Ulcerative colitis (UC) results from a complex interplay between the environment, gut microbiota, host genetics, and immunity. Runt-related transcription factor 3 (RUNX3) regulates Th1/Th2 balance and, thus, the synthesis of cytokines and inflammation. We aimed to analyze the dependence of RUNX3 promoter 2 (P2) methylation level on: age, sex, body mass index (BMI), C-reactive protein (CRP), serum albumin, disease duration, Pediatric Ulcerative Colitis Activity Index (PUCAI), the Paris classification, and exposure to medications. This multicenter, cross-sectional study recruited hospitalized children with UC. Methylation of RUNX3 P2 was measured with methylation-sensitive restriction enzymes in the whole blood DNA. Sixty-four children were enrolled, with a mean age of 14.5 ± 2.8 years. Half of them were female (51.6%), and the average BMI Z-score was -0.44 ± 1.14. The mean methylation of RUNX3 P2 was 54.1 ± 13.3%. The methylation level of RUNX3 P2 did not correlate with age, sex, nutritional status, CRP, albumin, PUCAI, or the extent of colitis (Paris E1-E4). RUNX3 P2 methylation did not differ between patients recruited within two and a half months of diagnosis and children who had UC for at least a year. Current or past exposure to biologics, immunosuppressants, or steroids was not associated with RUNX3 P2 methylation. Methylation of RUNX3 promoter 2 in whole blood DNA does not seem to be associated with the characteristics of UC in children.

Keywords: DNA methylation; RUNX3; methylation-sensitive restriction enzyme; ulcerative colitis.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Biological Products
  • C-Reactive Protein / genetics
  • C-Reactive Protein / metabolism
  • Child
  • Colitis, Ulcerative* / genetics
  • Core Binding Factor Alpha 3 Subunit / genetics
  • Core Binding Factor Alpha 3 Subunit / metabolism
  • Cross-Sectional Studies
  • Cytokines / metabolism
  • DNA Methylation*
  • Female
  • Humans
  • Immunosuppressive Agents
  • Male
  • Promoter Regions, Genetic
  • Serum Albumin / metabolism
  • Transcription Factor 3 / metabolism

Substances

  • Biological Products
  • Core Binding Factor Alpha 3 Subunit
  • Cytokines
  • Immunosuppressive Agents
  • Runx3 protein, human
  • Serum Albumin
  • Transcription Factor 3
  • C-Reactive Protein

Supplementary concepts

  • Pediatric ulcerative colitis

Grants and funding

This research was funded from a grant by the Polish National Science Center (no. 2017/25/B/NZ5/02783 awarded to J.W.).