Relationship of periodic methylation patterns in the gastric mucosa and periodic stem cell replacement.

Abstract

333 Background: The role of Helicobacter pylori-associated methylation in the inactivation of tumour-suppressor genes has been previously investigated. However, the relationship between H. pylori-associated methylation and gene inactivation is unclear. Stem cells are replaced periodically every 8 years in the gastrointestinal mucosa. Hence, age-related methylation in the gastric mucosa was studied to understand the stabilization of new stem cell phenotypes. Methods: Endoscopic biopsy specimens of the antral mucosa were obtained from 148 H. pylori-negative and 124 H. pylori-positive subjects. The methylation-variable sites of 4 housekeeping genes ( CDH1, ARRDC4, MMP2, and CDKN2A) and 2 stomach-specific genes ( TFF2 and TFF3) were examined using radioisotope-labelled methylation-specific polymerase chain reaction. Age-related methylation was evaluated at an interval of 2 years. Results: The 4 housekeeping genes were more frequently methylated in H. pylori-positive subjects than in H. pylori-negative subjects. Periodic changes in the housekeeping gene methylation were obscure. TFF2, which is highly expressed in the stomach, was periodically methylated to attain peaks at the age of 40–41, 48–49, 56–57, and 64–65 years in both H. pylori-negative and -positive subjects. TFF3, which is weakly expressed in the stomach, was methylated at the age of 46–47, 54–55, 66–67, and 72–73 years in H. pylori-negative subjects. The methylation of stomach-specific genes periodically fluctuated approximately at 8-year intervals in the gastric mucosa. Conclusions: Periodic methylation changes in the gastric mucosa may be used to estimate the replacement of new stem cells.