Association of Polymorphisms of NOD2, TLR4 and CD14 Genes with Susceptibility to Gastric Mucosa-associated Lymphoid Tissue Lymphoma

Background: The clinical course of H elicobacter pylori infection is highly variable and is influenced by both microbial and host factors, including the genetic composition of the infecting strains and variations in the host immune responses. A genetic risk profile for gastric cancer has been identified, but genetic susceptibility to develop gastric mucosa-associated lymphoid tissue (MALT) lymphoma is unclear. The aim of this study was to evaluate the relationship between NOD2, TLR4 and CD14 genetic polymorphisms and the development of gastric MALT- lymphoma. Material s and Methods: Fifty-six patients with primary gastric MALT lymphoma and 51 patients with H. pylori infection were enrolled in th is study. The polymorphisms were detected by the PCR-restriction fragment length polymorphism (RFLP) method of allele- specific PCR. Results: No polymorphisms in the NOD2 and TLR4 genes were found to be associated with the development of gastric MALT lymphoma. Carriers of the CD14 gene -159T allele had a marginally increased risk of developing gastric MALT lymphoma than the controls (p=0.042). Conclusion: The -159C/T genetic polymorphism of the CD14 gene may be implicated in the development of gastric MALT lymphoma. Helicobacter pylori is a Gram-negative bacterium which colonizes the stomach due to its ability to survive in the highly acidic environment and penetrate the mucus gel layer. This allows close contact with the underlying gastric epithelial cells. H. pylori induces an immunologically mediated inflammation in the gastric mucosa which may lead to the development of chronic active gastritis, duodenitis, peptic ulcer disease, gastric atrophy, gastric carcinoma and/or gastric mucosa-associated lymphoid tissue (MALT) lymphoma (1). Studies have shown that almost two out of three people worldwide are infected with H. pylori . The prevalence of the infection is low in the developed world but it is overwhelming in Third World countries where nearly 90% of the general population is infected. Whereas most infected individuals are asymptomatic, the clinical course of H. pylori infection is highly variable and is influenced by both microbial and host factors, including the genetic composition of the infecting strains and the genetic make-up of the host, and especially by variations in the host immune responses (2).