The Relation Between Host TLR9 -1486T/C, rs187084 Gene Polymorphisms and H. Pylori cagA, sodB, hsp60 and vacA Virulence Genes Among Gastric Cancer Patients

Abstract

Purpose: To identify different genotypes of TLR9 -1486T/C (rs187084) in patients with gastric cancer and reveal their relation to H. pylori virulence genes (cagA, sodB, hsp60 and vacA). Methods: Patients with gastric cancer were recruited to our study, diagnosed both endoscopically and histo-pathologically. H. pylori strains were isolated from gastric samples by culture and PCR amplification of glmM gene. Virulence genes of H. pylori; cagA, sodB, Hsp60 and vacA, were detected by multiplex PCR. Blood samples were used for genotyping of TLR9 -1486T/C (rs187084) by PCR-RFLP. Results: Out of 132 patients with gastric cancer, 106 (80.3%) were positive for H. pylori by both culture and PCR. Similar number of healthy participants were recruited as controls. The prevalence of virulence genes among the isolated H. pylori were 90.6%, 70.8%, 83.0% and 95.3% for cagA, sodB, hsp60 and vacA respectively. The vacA gene alleles had a prevalence of 95.3% for vacAs1/s2, 52.8% for vacAm1 and 42.5% for vacAm2. The CC genotype of TLR9 -1486T/C had a significantly higher frequency in gastric cancer patients when compared to healthy participants (P = 0.045). Furthermore, the CC genotype demonstrated a significantly higher association with H. pylori strains carrying sodB, hsp60 and vacAm1 virulence genes (P = 0.021, P = 0.049 and P = 0.048 respectively). Conclusions: Patients with CC genotype of TLR9 -1486T/C (rs187084) are at higher risk for development of gastric cancer and its co-existence with H. pylori strains carrying sodB, hsp60 or vacAm1 virulence genes might have a synergistic effect in development of gastric cancer.