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

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. View Full-Tex