Helicobacter pylori virulence genes and host IL-1RN and IL-1beta genes interplay in favouring the development of peptic ulcer and intestinal metaplasia.
Helicobacter pylori infection outcome might depend on genotypic polymorphisms of both the bacterium and the host. We ascertained: (1) the functionality of H. pylori oipA gene; (2) the polymorphism of the hostinterleukin (IL-1beta) gene (-31 C/T) and of the IL-1RN gene (intron 2 VNTR); (3) the association between the above genes and the histological and pathological outcome of H. pylori infection. One hundred and sixty-five H. pylori positive and 137 H. pylori negative subjects (23 gastric adenocarcinoma, 58 peptic ulcer, 221 gastritis) were studied. oipA was sequenced, IL-1beta was RFLP analysed. Antral and body mucosal biopsies were histologically evaluated. Functional oipA genes were correlated with cagA gene; both genes were significantly associated with gastritis activity, peptic ulcer and gastric adenocarcinoma. In these patients heterozygousIL-1RN 1/2 and IL-1beta C/T genotypes were more frequent than in gastritis patients. Intestinal metaplasia was associated with cagA, functional oipA and IL-1RN 2 allele. In conclusion, peptic ulcer and the preneoplastic intestinal metaplasia are associated with H. pylori virulence genes and with IL-1RN 2 host allele. An interplay between bacterial virulence factors and cytokines genotypes, is probably the main route causing H. pylori infection to lead to benign mild disease, benign severe disease or preneoplastic lesions.
Zambon
C-F
CF
Department of Laboratory Medicine, University of Padova, Italy.
Basso
D
D
Navaglia
F
F
Germano
G
G
Gallo
N
N
Milazzo
M
M
Greco
E
E
Fogar
P
P
Mazza
S
S
Di Mario
F
F
Basso
G
G
Rugge
M
M
Plebani
M
M
D000230:Adenocarcinoma / Q000235:genetics / Q000382:microbiology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000235:genetics; D004724:Endoscopy; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D005838:Genotype; D016480:Helicobacter pylori / Q000235:genetics* / Q000472:pathogenicity*; D006579:Heterozygote; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics*; D008297:Male; D008679:Metaplasia / Q000235:genetics* / Q000382:microbiology*; D008875:Middle Aged; D010437:Peptic Ulcer / Q000382:microbiology*; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012795:Sialoglycoproteins / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics / Q000382:microbiology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori