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Association of TLR4 Polymorphisms, Expression, and Vitamin D with Helicobacter pylori Infection.

ABSTRACT: Helicobacter pylori (H. pylori) infection is the strongest recognized risk factor for gastric adenocarcinoma. Since previous observations have shown that polymorphisms in innate immune system genes, as well as vitamin D (VitD) levels, could modify the risk of infection with Helicobacter pylori (H. pylori), we analyzed the relation between single nucleotide polymorphisms (SNPs) in TLRs (TLR1, TLR2, TLR4) CD14, RUNX3 and VitD levels with H. pylori infection. A case-control study on four hundred sixty Lebanese individuals was conducted. Eleven SNPs in total were genotyped and gene expression analysis using real-time PCR was performed in white blood cells of a subsample of eight individuals. A total of 49% of the participants were affected. Although no direct association was found between the SNPs and H. pylori infection, rs4986790G>A and rs4986791T>C in TLR4 were negatively associated with VitD levels (? = -0.371, p = 5 × 10-3 and ? = -0.4, p = 2 × 10-3, respectively), which was negatively associated with H. pylori infection (OR = 0.01, p < 1 × 10-3). TLR4 expression was 3× lower in individuals with H. pylori compared with non-infected (p = 0.01). TLR4 polymorphisms, expression, and VitD could be implicated in H. pylori infection and further development of gastric adenocarcinoma.

SUBMITTER: Assaad S

PROVIDER: S-EPMC6463146 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Association of TLR4 Polymorphisms, Expression, and Vitamin D with Helicobacter pylori Infection.

Assaad Shafika S Costanian Christy C Jaffal Lama L Tannous Fida F Stathopoulou Maria G MG El Shamieh Said S

Journal of personalized medicine 20190111 1

Helicobacter pylori (H. pylori) infection is the strongest recognized risk factor for gastric adenocarcinoma. Since previous observations have shown that polymorphisms in innate immune system genes, as well as vitamin D (VitD) levels, could modify the risk of infection with Helicobacterpylori (H. pylori), we analyzed the relation between single nucleotide polymorphisms (SNPs) in TLRs (TLR1, TLR2, TLR4) CD14, RUNX3 and VitD lev ...[more]

PMID: 30641993

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Project description:AimTo investigate Helicobacter pylori (H. pylori) CagA diversity and to evaluate the association between protein polymorphisms and the occurrence of gastric pathologies.MethodsOne hundred and twenty-two clinical isolates of H. pylori cultured from gastric biopsies obtained from Colombian patients with dyspepsia were included as study material. DNA extracted from isolates was used to determine cagA status, amplifying the C-terminal cagA gene region by polymerase chain reaction. One hundred and six strains with a single amplicon were sequenced and results were used to characterize the 3' variable region of the cagA gene. To establish the number and type of tyrosine phosphorylation motifs Glutamine acid-Proline-Isoleucine-Tyrosine-Alanine (EPIYA) bioinformatic analysis using Amino Acid Sequence Analyzer-Amino Acid Sequence Analyzer software was conducted. Analysis of the association between the number of EPIYA motifs and the gastric pathology was performed using chi(2) test and analysis of the presence of EPIYA-C motifs in relation to the pathology was made by logistic regression odds ratios. Comparisons among EPIYA types found and those reported in GenBank were performed using a proportion test in Statistix Analytical Software version 8.0.ResultsAfter amplification of the 3' of the cagA gene, 106 from 122 isolates presented a single amplicon and 16 showed multiple amplicons. As expected, diversity in the size of the cagA unique fragments among isolates was observed. The 106 strains that presented a single amplicon after 3' cagA amplification came from patients with gastritis (19 patients), atrophic gastritis (21), intestinal metaplasia (26), duodenal ulcer (22) and gastric cancer. DNA sequence analysis showed that the differences in size of 3' cagA unique fragments was attributable to the number of EPIYA motifs: 1.9% had two EPIYA motifs, 62.3% had three, 33.0% had four and 2.8% had five motifs. The majority of tested clinical strains (62.3%) were found to harbor the ABC combination of EPIYA motifs and a significant statistical difference was observed between the frequencies of ABCC tyrosine phosphorylation motifs and Western strains sequences deposited in GenBank.ConclusionThe present report describes a lack of association between H. pylori CagA-protein polymorphisms and pathogenesis. ABCC high frequency variations compared with Western-strains sequences deposited in GenBank require more investigation.

Dataset Information

Association of TLR4 Polymorphisms, Expression, and Vitamin D with Helicobacter pylori Infection.

Publications

Association of TLR4 Polymorphisms, Expression, and Vitamin D with Helicobacter pylori Infection.

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