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Persistence of a component of DNA methylation in gastric mucosae after Helicobacter pylori eradication

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Abstract

Background

Helicobacter pylori (HP) infection potently induces aberrant DNA methylation in gastric mucosae, and its accumulation is associated with gastric cancer risk. Cross-sectional analysis of methylation levels (fraction of methylated DNA molecules) and temporal analysis of methylation incidence suggested that methylation levels decrease after HP infection discontinues. We aimed to demonstrate the decrease in methylation levels.

Methods

Thirty-five patients with HP infection who had undergone curative endoscopic resection and 11 healthy volunteers were recruited. Methylation levels were quantified by real-time methylation-specific PCR. Histology was evaluated according to the updated Sydney System.

Results

In the 20 patients with successful eradication, the FLNc methylation level, along with infiltration of inflammatory cells, decreased from 0.6 to 0.4% at 6 weeks (P = 0.049) and remained low at 1 year. The THBD methylation level (30.1%) remained high at 6 weeks, but decreased to 19.0% at 1 year (P = 0.0032). Nine healthy volunteers with successful eradication tended to show a decrease of both FLNc and THBD at 6 weeks. However, the methylation levels after the decrease were still higher than those of healthy individuals without HP infection. In the 15 patients with persistent infection, the methylation levels remained the same. Before eradication, the THBD methylation level correlated with the degree of inflammatory cell infiltration (P < 0.05).

Conclusions

Methylation levels in gastric mucosae decreased to certain levels after HP eradication in profiles unique to individual markers. Involvement of chronic inflammation in methylation induction was suggested.

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Acknowledgments

This study was supported by Grants-in-Aid for Pioneering Basic Research and for the Third-term Comprehensive Cancer Control Strategy from the Ministry of Health, Labor and Welfare, Japan. T.A. is a recipient of a Research Resident Fellowship from the Foundation for Promotion of Cancer Research.

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Correspondence to Toshikazu Ushijima.

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535_2009_142_MOESM1_ESM.ppt

Changes of the FLNc methylation level in the three biopsy sites (antrum, middle gastric body, and upper gastric body in the lesser curvature). In the successful eradication group, FLNc methylation levels in the middle and upper gastric bodies showed significant decreases (PPT 264 kb)

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Nakajima, T., Enomoto, S., Yamashita, S. et al. Persistence of a component of DNA methylation in gastric mucosae after Helicobacter pylori eradication. J Gastroenterol 45, 37–44 (2010). https://doi.org/10.1007/s00535-009-0142-7

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  • DOI: https://doi.org/10.1007/s00535-009-0142-7

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