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

Shafika Assaad, Christy Costanian, Lama Jaffal, Fida Tannous, Maria G Stathopoulou, Said El Shamieh
Journal of Personalized Medicine 2019 January 11, 9 (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 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.


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