title: 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.
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.
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Kuei-Hsiang
authors.initials: KH
authors.lastname: Hung
authors.forename: Hunt-Wen
authors.initials: HW
authors.lastname: Hung
authors.forename: Hsiao-Bai
authors.initials: HB
authors.lastname: Yang
authors.forename: Cheng-Chan
authors.initials: CC
authors.lastname: Lu
authors.forename: Jiunn-Jong
authors.initials: JJ
authors.lastname: Wu
authors.forename: Bor-Shyang
authors.initials: BS
authors.lastname: Sheu
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000235:genetics* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000502:physiology; D006801:Humans; D007422:Intestines / Q000276:immunology / Q000473:pathology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008679:Metaplasia / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012727:Sex Characteristics; D013270:Stomach / Q000276:immunology / Q000473:pathology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9