E266K CARD4/NOD1 and toll-like receptor 4 gene polymorphisms in Helicobacter pylori-infected patients with duodenal ulcer or gastritis

Background: Helicobacter pylori (HP) can be recognized in epithelial cells by the intracellular pathogen receptor NOD1 or extracellular LPS detecting toll-like receptor 4 (TLR4).

The aim was to evaluate the frequency of NOD1 and TLR4 gene polymorphism in HP-infected patients with duodenal ulcer (DU) and gastritis.

Patients. 131 HP-positive patients with dyspeptic symptoms were examined by gastroduodenoscopy. HP positivity was detected by 13C-UBT and histopathology. DU was found in 58 and gastritis in 73 patients.

Methods. E266K CARD4/NOD1 (G to A) was determined by RFLP, and the TLR4 (ASP/299/Gly and Thr/399/Ile) gene polymorphism by melting point analysis with a real-time PCR method. Statistical analysis was performed by using the Fisher exact test or Χ2 test as appropriate.

Results: AA homozygote mutant variants of NOD1 were detected in 12 of 58 HP-positive patients with DU (20%) vs. 5 of 73 HP-positive patients with gastritis (6.8%), the difference being significant (p=0.034, OR: 3.42, 95% CI=1.184–2.519). Conversely, the G alelle was significantly more frequent in patients with gastritis 76% than in DU patients (62%) (p=0.014, OR: 2.992, 95% CI=1.574–5.789). However, no significant correlation in the frequency of the TLR4 gene polymorphism could be revealed between these two groups. The genotype frequency of AG heterozygotes concerning gene polymorphism ASP/299/Gly was 13.8% in the patients with gastritis vs. 8.6% in DU patients (p=0.490). Similarly there was 13.2% frequency of CT heterozygotes concerning the Thr/399/Ile gene polymorphism in the patients with gastritis vs. 8.66% in DU patients (p=0.568).

Conclusion: E266K CARD4/NOD1, but not the TLR4 gene polymorphism increases the risk of peptic ulceration in HP-positive patients. Host factors including intracellular pathogen receptors play an important role in the severity of the HP-induced gastric mucosal damage.