Polymorphisms at Locus 4p14 of Toll-Like Receptors TLR-1 and TLR-10 Confer Susceptibility to Gastric Carcinoma in Helicobacter pylori Infection

PLoS One. 2015 Nov 11;10(11):e0141865. doi: 10.1371/journal.pone.0141865. eCollection 2015.

Abstract

Helicobacter pylori (H. pylori) -induced gastric inflammation impacts the functions of leptin- and ghrelin-producing cells in the gastroduodenum. Inflammation resulting from H. pylori sensing via Toll-like receptors (TLRs) and the associated downstream signaling largely remain ambiguous. Here, we investigated the role of gut hormones, pro-inflammatory cytokines and single nucleotide polymorphisms (SNPs) associated with TLR 4p14 in H. pylori disease in 30 subjects with non-ulcer dyspepsia (NUD), 40 with peptic ulcer disease (PUD) and 15 with gastric cancer (GC) subjects positive and negative for H. pylori infection. The level of pro-inflammatory cytokines was directly proportional to the severity of gastritis, and disease status influenced the levels of gut hormones and pro-inflammatory cytokines. TLR-1 SNPs rs4833095 and TLR-10 SNPs rs10004195 and were directly associated with H. pylori disease, and were up-regulated in the presence of H. pylori in a genotype-independent manner. We concluded that TLR-1 rs4833095 and TLR10 rs10004195 confer susceptibility to development of gastroduodenal disease, especially GC in H.pylori disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Chromosomes, Human, Pair 4*
  • Cytokines / blood
  • Female
  • Genetic Predisposition to Disease*
  • Helicobacter Infections / complications*
  • Helicobacter Infections / microbiology
  • Helicobacter pylori / isolation & purification*
  • Humans
  • Leptin / blood
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Receptor, Insulin / blood
  • Stomach Neoplasms / complications
  • Stomach Neoplasms / genetics*
  • Toll-Like Receptor 1 / genetics*
  • Toll-Like Receptor 10 / genetics*
  • Young Adult

Substances

  • Cytokines
  • Leptin
  • Toll-Like Receptor 1
  • Toll-Like Receptor 10
  • Receptor, Insulin

Grants and funding

This work was supported by a grant from the University of Malaya – Ministry of Education (UM-MOE) High Impact Research (HIR) (Grant. No. UM.C/625/1/HIR/MOE/CHAN-13/4; Account No. H-50001-A000029). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.