Host single nucleotide polymorphisms of MMP-9 -1562/TIMP-1 372 have gender differences in the risk of gastric intestinal metaplasia after Helicobacter pylori infection

Helicobacter. 2009 Dec;14(6):580-7. doi: 10.1111/j.1523-5378.2009.00717.x.

Abstract

Background: Helicobacter pylori infection causes chronic gastric inflammation and intestinal metaplasia (IM), related with deregulation of Wnt pathway and over-expressions of COX-2, matrix metalloproteinase (MMP), and tissue inhibitors of matrix metalloproteinase (TIMP). We thus test the host genomic predispositions related to the risk of IM after H. pylori infection.

Methods: We enrolled 296 H. pylori-infected patients to provide gastric biopsies for histology and genomic DNA for genotypes of single nucleotide polymorphisms (SNPs), including APC, COX-2, IL-1B, IL-1RN, IL-10, MMP-2, MMP-9, TIMP-1, and TIMP-2 determined by sequence specific oligonucleotide probe, sequence specific primers, restriction fragment length polymorphism, or real-time polymerase chain reaction.

Results: There was no association between the presence of IM and SNPs in APC, COX-2, IL-1B, IL-1RN, IL-10, MMP-2, and TIMP-2. The risk of IM was increased up to 2.29-folds in males with TIMP-1 372 C, and 3.03-fold in females with T carrier (p < .05). The combination genotype of MMP-9 -1562/TIMP-1 372 as CC/C and CT/T in males had a 4.5-fold increased risk of IM, as compared to CC/T (p < .05). Females with such combination genotype as CC/T-carrier had a 3-fold risk of IM than males with CC/T (p < .05). In contrast, males' combination genotype as CC/C had a 3-fold risk of IM than females with CC/CC (p = .05).

Conclusions: The host MMP-9 -1562/TIMP-1 372 SNPs had gender differences in the risk of IM after H. pylori infection, and could possibly serve as a host factor to identify the risk group harboring gastric precancerous changes after H. pylori infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Female
  • Genetic Predisposition to Disease
  • Helicobacter Infections / genetics*
  • Helicobacter Infections / immunology
  • Helicobacter Infections / microbiology
  • Helicobacter Infections / pathology
  • Helicobacter pylori / physiology
  • Humans
  • Intestines / immunology
  • Intestines / pathology*
  • Male
  • Matrix Metalloproteinase 9 / genetics*
  • Metaplasia / genetics
  • Metaplasia / immunology
  • Metaplasia / microbiology
  • Metaplasia / pathology
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Sex Characteristics
  • Stomach / immunology
  • Stomach / pathology*
  • Tissue Inhibitor of Metalloproteinase-1 / genetics*

Substances

  • Tissue Inhibitor of Metalloproteinase-1
  • Matrix Metalloproteinase 9