Age-related methylation patterning of housekeeping genes and tissue-specific genes is distinct between the stomach antrum and body

Epigenomics. 2013 Jun;5(3):283-99. doi: 10.2217/epi.13.17.


Aim: The methylation-variable sites around CpG islands are frequently overmethylated in Helicobacter pylori-infected stomachs. Age-related patterns of the overmethylation changes were compared between the fast-growing antrum cells and the slow-growing body cells.

Materials & methods: A total of 316 H. pylori-positive tissues and 380 H. pylori-negative tissues were obtained by endoscopic biopsy. The methylation-variable sites of ten housekeeping genes and nine tissue-specific genes were semiquantitatively analyzed, based on the ten-level classification of methylation-specific PCR intensity. The overmethylated genes were scored when their methylation levels were higher than an intermediate level of each gene common in the H. pylori-negative mucosa.

Results: The age-dependent methylation level of the inactive APC gene observed similarly in the antrum and the body was used as an age standard of methylation variation in a biopsy tissue. The overmethylation of housekeeping genes and stomach-specific genes rapidly increased to a high plateau frequency in the young-aged APC methylation cases (mean age: 43 years) in the H. pylori-positive antrum. In the H. pylori-positive body, most of the overmethylated housekeeping genes slowly increased to a peak frequency in the middle-aged APC methylation cases (mean age: 53 years). The housekeeping gene pairs showed high correlations (Spearman's correlation coefficient > 0.4) in both the antrum and the body.

Conclusion: The overmethylation of housekeeping genes rapidly and slowly increased to a high frequency in concordance with a rapid and slow growth of epithelial cells in the H. pylori-infected stomach.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aging*
  • CpG Islands
  • DNA Methylation*
  • Gastric Mucosa / metabolism*
  • Genes, Essential / genetics*
  • Helicobacter Infections / genetics
  • Helicobacter Infections / metabolism
  • Helicobacter Infections / microbiology
  • Helicobacter pylori
  • Humans
  • Middle Aged
  • Pyloric Antrum / metabolism*
  • Retroelements / genetics


  • Retroelements