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

Shafika Assaad,Said El Shamieh,Maria G Stathopoulou,Christy Costanian,Lama Jaffal,Fida Tannous

doi:10.3390/jpm9010002

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 (β = −0.371, p = 5 × 10−3 and β = −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.

Highlights

Helicobacter pylori (H. pylori) infection has high incidence rates worldwide and is the major cause of several gastrointestinal symptoms, ranging from mild gastritis to gastric adenocarcinoma [1]
Controls were first examined through the same procedure and not found to be carrying H. pylori; in addition, they were matched in terms of age, gender, body mass index (BMI) categories, marital status and alcohol consumption
Individuals infected with H. pylori were vitamin D (VitD)-deficient, whereas non-affected individuals had normal VitD levels (p < 1 × 10−3, Table 1)

Summary

Introduction

Helicobacter pylori (H. pylori) infection has high incidence rates worldwide and is the major cause of several gastrointestinal symptoms, ranging from mild gastritis to gastric adenocarcinoma [1]. It has been estimated that up to half of the world’s population harbor this infection in their stomach [1]. Population-based studies report that developing countries have a higher prevalence rate of H. pylori than their developed counterparts [1]. Using data from a nationally representative, cross-sectional study on Lebanese adults, Naja et al found that the prevalence of H. pylori infection was 52%, a rate comparable to other developing countries [2].

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