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

Abstract

Helicobacter pylori (<i>H. pylori</i>) 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 <i>Helicobacter</i><i>pylori</i> (<i>H. pylori</i>), we analyzed the relation between single nucleotide polymorphisms (SNPs) in <i>TLRs</i> (<i>TLR1</i>, <i>TLR2</i>, <i>TLR4</i>) <i>CD14</i>, <i>RUNX3</i> and VitD levels with <i>H. pylori</i> 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 <i>H. pylori</i> infection, rs4986790G>A and rs4986791T>C in <i>TLR4</i> were negatively associated with VitD levels (β = -0.371, <i>p</i> = 5 × 10^-3 and β = -0.4, <i>p</i> = 2 × 10^-3, respectively), which was negatively associated with <i>H. pylori</i> infection (OR = 0.01, <i>p</i> < 1 × 10^-3). <i>TLR4</i> expression was 3× lower in individuals with <i>H. pylori</i> compared with non-infected (<i>p</i> = 0.01). <i>TLR4</i> polymorphisms, expression, and VitD could be implicated in <i>H. pylori</i> infection and further development of gastric adenocarcinoma.