title: The association of interleukin-18 promoter polymorphisms and serum levels with duodenal ulcer, and their correlations with bacterial CagA and VacA virulence factors.
abstract: BACKGROUND
  We analyzed the impact of interleukin (IL)-18 promoter polymorphisms on IL-18 serum levels in Helicobacter pylori-infected duodenal ulcer (DU) patients and healthy asymptomatic (AS) carriers. We also aimed to determine the association of the H. pylori virulence factors CagA and VacA antibodies with serum concentrations of IL-18 in order to elucidate any correlation between them.
  
  
  METHODS
  Three groups of patients were enrolled: DU patients (67 individuals), AS carriers (48 individuals), and H. pylori-negative subjects (26 individuals). Serum concentrations of IL-18 were determined by ELISA. Patient sera were tested by Western blot method to determine the presence of serum antibodies to bacterial CagA and VacA. Genotyping of IL-18 promoter polymorphisms at positions - 137G/C and - 607C/A were performed by allele-specific primer PCR protocol.
  
  
  RESULTS
  Our study revealed that serum IL-18 levels are positively influenced by CagA-positive H. pylori strains, so that maximum levels of IL-18 were detected in DU patients with the CagA(+) phenotype, regardless of the presence of the anti-VacA antibody. Regarding IL-18 promoter polymorphisms, the AA genotype and A allele at position - 607C/A were found to be significantly lower in DU patients than in AS carriers and H. pylori-negative subjects (p = 0.032 and 0.043, respectively).
  
  
  CONCLUSIONS
  The IL-18 - 607C variant was associated with higher levels of serum IL-18 and an increased risk of DU. Moreover, our findings indicated that serum concentrations of IL-18 were influenced by CagA factor, irrespective of the VacA status, suggesting that high levels of IL-18 in CagA-positive subjects predisposes to susceptibility to DU.
authors.affiliation: Department of Clinical Biochemistry, School of Medicine, Zabol University of Medical Sciences, Zabol, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Rezaeifar
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Eskandari-Nasab
authors.forename: Mehdi
authors.initials: M
authors.lastname: Moghadampour
authors.forename: Eslam
authors.initials: E
authors.lastname: Kharazi-Nejad
authors.forename: Seyed-Shahab-Adin
authors.initials: SS
authors.lastname: Hasani
authors.forename: Abolghasem
authors.initials: A
authors.lastname: Asadi-Saghandi
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hadadi-Fishani
authors.forename: Adel
authors.initials: A
authors.lastname: Sepanjnia
authors.forename: Behrooz
authors.initials: B
authors.lastname: Sadeghi-Kalani
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D015153:Blotting, Western; D004198:Disease Susceptibility; D004381:Duodenal Ulcer / Q000453:epidemiology* / Q000382:microbiology; D004797:Enzyme-Linked Immunosorbent Assay; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications / Q000276:immunology / Q000382:microbiology; D016480:Helicobacter pylori / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D020382:Interleukin-18 / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D044967:Serum / Q000737:chemistry / Q000276:immunology; D037521:Virulence Factors / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D020382:Interleukin-18; C074689:VacA protein, Helicobacter pylori; D037521:Virulence Factors; C080866:cagA protein, Helicobacter pylori