Effect of RANTES promoter genotype on the severity of intestinal metaplasia in Helicobacter pylori-infected Japanese subjects

Dig Dis Sci. 2009 Jun;54(6):1247-52. doi: 10.1007/s10620-008-0497-2. Epub 2008 Oct 29.

Abstract

Background: A complex interaction of host genetic and environmental factors may be relevant in the development of Helicobacter pylori (H. pylori)-related gastro-duodenal diseases. RANTES is a potent chemoattractant peptide for memory T lymphocytes and eosinophils, and has been shown to be enhanced in H. pylori-infected gastric mucosa. We aimed to clarify the effect of RANTES functional promoter polymorphism on the risk of gastro-duodenal diseases in a Japanese population.

Methods: Four hundred and eighty-three subjects, comprising 106 gastric ulcer, 52 duodenal ulcer, and 325 non-ulcer subjects, were included in this study. Restriction fragment length polymorphism (RFLP) analysis was performed for polymorphisms at -28 C/G in the RANTES gene promoter region. Gastritis scores of antral gastric mucosa were assessed according to the updated Sydney system.

Results: There were no significant differences in the RANTES promoter genotype distributions among non-ulcer subjects, ulcer patients, and gastric and duodenal ulcers. However, the degree of intestinal metaplasia was significantly lower among G carriers in H. pylori-infected subjects aged 60 years or older (C/C vs. G carriers; 1.28 +/- 1.02 vs. 0.83 +/- 0.89, P = 0.0357). In addition, we also found that the same genotype held a lower risk of more severe intestinal metaplasia in H. pylori-infected female subjects (C/C vs. G carriers; 0.91 +/- 1.03 vs. 0.41 +/- 0.73, P = 0.0443).

Conclusion: The polymorphism of RANTES promoter is not associated with the susceptibility to peptic ulcer diseases, but the -28 G carrier is associated with a reduced risk of developing more severe intestinal metaplasia in H. pylori-positive subjects aged 60 years and older and in female subjects.

MeSH terms

  • Adult
  • Aged
  • Aging
  • Chemokine CCL5 / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Helicobacter Infections / complications*
  • Helicobacter pylori*
  • Humans
  • Intestinal Diseases / genetics*
  • Intestinal Diseases / microbiology
  • Male
  • Metaplasia / genetics*
  • Metaplasia / microbiology
  • Middle Aged
  • Polymorphism, Genetic
  • Promoter Regions, Genetic / genetics*
  • Sex Characteristics

Substances

  • CCL5 protein, human
  • Chemokine CCL5