Association of IL1B -511C/-31T haplotype and Helicobacter pylori vacA genotypes with gastric ulcer and chronic gastritis

Abstract

BackgroundThe association between proinflammatory cytokine gene polymorphisms and gastric diseases related to Helicobacter pylori varies by population and geographic area.Our objective was to determine if the IL-1B -511 T>C and -31 C>T polymorphisms and H. pylori vacA genotypes are associated with risk of chronic gastritis and gastric ulcer in a Mexican population.MethodsWe conducted endoscopic studies in 128 patients with symptoms of dyspepsia. We took two biopsies from the body, antrum, or ulcer edge from each patient, and classified our histopathological findings according to the Sydney System. H. pylori infection and vacA genotyping were accomplished via PCR from total DNA of the gastric biopsies. We confirmed the presence of anti-H. pylori serum IgG and IgM in 102 control subjects. In both case subjects and control subjects, the IL-1B -511 T>C polymorphism was genotyped by PCR-RFLPs and the IL-1B -31 C>T polymorphism was genotyped by pyrosequencing.ResultsSixty-two point seven (62.7%) of the 102 control subjects were H. pylori-seropositive. Among the case subjects, 100 were diagnosed with chronic gastritis and 28 with gastric ulcer. We found that 77% of the patients with chronic gastritis and 85.7% of the patients with gastric ulcer were H. pylori-positive. The predominant H. pylori genotype was vacA s1m1 (58.4%) and the most frequent subtype was vacA s1. The -511 TC, (rs16944 -511 T>C) genotype and the -511C allele were associated with chronic gastritis (OR = 3.1, 95% CI = 1.4-6.8 and OR = 3.0, 95% CI = 1.4-6.0, respectively). The subjects carrying -31T (rs1143627 -31 C>T) were found to be at a higher risk of having chronic gastritis (OR = 2.8, 95% CI = 1.3-5.8). The IL-1B -511C/-31T haplotype was associated with chronic gastritis (OR = 2.1, 95% CI = 1.2-3.8) but not with gastric ulcer.ConclusionsThe H. pylori vacA genotypes identified herein were similar to those reported for other regions of Mexico. The vacA s1m1 genotype was not associated with gastric ulcer. In the southern Mexican population, the IL-1B -511C and -31T alleles and the -511C/-31T and -511T/-31T haplotypes are associated with increased risk of chronic gastritis and gastric ulcer.

Association of Cytokine Gene Polymorphisms with Gastritis in a Kazakh Population

“…In most cases the infection Helicobacter pylori is asymptomatic. H. pylori infectivity is highly dependent on ethnicity and geographical region (Gehmert et al, 2009;Martinez-Carrillo et al, 2010).…”

“…Although the majority of infected people don't have symptoms of stomach diseases, persistent colonization and chronic inflammation increase the risk of gastritis (Gehmert et al, 2009;Martinez-Carrillo et al, 2010).…”

Relationship of interleukin-1B gene promoter region polymorphism with Helicobacter pylori infection and gastritis

“…The presence of the T allele at position -511 and C allele at position -31 is associated with high levels of IL-1 [18]. IL-1 is a powerful inhibitor of gastric acid secretion; on a molar basis, IL-1 is estimated to be 100-fold more potent than proton pump inhibitors and 6000-fold more potent than H 2 receptor antagonists [16,40,41].…”

“…Genetic polymorphisms involved in the regulation of gastric acid secretion may to be associated with host susceptibility to the acquisition of H. pylori infection and to the development of gastric pathologies [18,36].…”

“…Three single nucleotide polymorphisms (SNPs) associated with high levels of IL-1 secretion have been reported in the IL-1B gene: a T-C base transition at position -31 and C-T base transitions at positions -511 and +3954 from the transcriptional start site [17][18][19]. Increased production of IL-1 in the gastric mucosa might result in the enhanced suppression of gastric acid secretion, as well as enhanced inflammation, allowing the expansion of H. pylori colonization from the gastric antrum to the corpus.…”