TLR5 Polymorphisms rs2072493, rs5744174, and rs5744168 Are Not Genetic Risk Factors for Chronic Helicobacter pylori Infection in Indian Tamils.

The incidence of Helicobacter pylori (H. pylori) infection and gastric cancer is on the rise in India, and the genetic factors influencing the increased susceptibility in Indian population remain obscure. Toll-like receptors (TLRs) play a major role in innate immune system and genetic polymorphisms affecting their function were reported to enhance the risk for H. pylori infection. Seventy-seven patients (n = 77) diagnosed with H. pylori infection and 230 healthy subjects were recruited in this study. The rs2072493, rs5744174, and rs5744168 polymorphisms within TLR5 gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Tetra-ARMS PCR genotyping techniques. Present study revealed that these studied polymorphisms are less frequent in south Indian Tamils and thus failed to confer a significant risk to develop chronic H. pylori infections. The distribution of ancestral allele of rs2072493 polymorphism conferred resistance to develop chronic H. pylori infection in our population (p = 0.024; OR  =  0.53; 95% CI: 0.3-0.91). The lesser incidence of polymorphic alleles suggests that the TLR5 gene is under genetic selection pressure to withstand the prevailing endemic infections among south Indian Tamils.

Genetic variants of TLR4 and TLR9 are risk factors for chronic Helicobacter pylori infection in South Indian Tamils.

Toll like receptors (TLRs) are a class of molecular pattern recognition receptors, elicits a strong inflammatory immune response against pathogens. Helicobacter pylori (H. pylori), a gram negative flagellate colonizes the human stomach, is responsible for the development of chronic gastritis and gastric carcinoma. The higher incidence of H. pylori infection and gastric cancer in South Indian Tamils demands a genetic study to unravel the influence of TLR4 and TLR9 polymorphisms associated with chronic H. pylori infection. In this study, 230 healthy individuals and 77 patients diagnosed with H. pylori infection were screened for TLR4 (rs1927914, rs4986790, rs4986791) and TLR9 (rs352140, rs34399053, rs150459369) polymorphisms by PCR-RFLP and ARMS-PCR. We observed that the individuals harboring heterozygous and homozygous polymorphic variants of TLR4 conferred a significant risk to develop chronic H. pylori infection and peptic ulcer disease [rs4986790 AG, p=0.001, OR-2.7, 95%CI: 1.5-5.03; GG, p=0.0006, OR-9.8, 95%CI: 2.4-39.4; rs4986791CT, p=0.0001, OR-7.2, 95%CI: 3.7-7.2; TT, p=0.0001, OR-7.9, 95%CI: 2.6-23.7]. Also, the heterozygous variant of TLR9 rs352140, favoured the persistence of the H. pylori infection [p=0.037, OR-1.87, 95%CI: 1.07-3.29]. Thus our findings suggest that TLR4 rs4986790, rs4986791 and TLR9 rs352140 polymorphisms are potential genetic risk factors influencing the disease susceptibility and clinical manifestation of chronic H. pylori infection in Indian Tamils.