Genetic polymorphisms of NOD1 and IL-8, but not polymorphisms of TLR4 genes, are associated with Helicobacter pylori-induced duodenal ulcer and gastritis.
BACKGROUND
Intracellular pathogen receptor NOD1 is involved in the epithelial cell sensing Helicobacter pylori, which results in a considerable interleukin (IL)-8 production. The aim of this study was to evaluate the relationship between NOD1 and IL-8 genetic polymorphisms and the development of H. pylori-induced gastritis and duodenal ulcer (DU), as compared with TLR4 polymorphisms.


METHODS
Eighty-five patients with DU and 135 patients with gastritis were enrolled in the study. Seventy-five serologically H. pylori-positive subjects without gastric or duodenal symptoms served as controls. The G796A (E266K) NOD1 polymorphism was determined by restriction fragment length polymorphism, and the -251 IL-8 polymorphism by amplification refractory mutation system method. The TLR4 (ASP/299/Gly and Thr/399/Ile) gene polymorphisms were examined by melting point analysis.


RESULTS
AA homozygote mutant variants of NOD1 were detected in 20% of the H. pylori-positive patients with DU versus 7% of H. pylori-positive patients with gastritis and versus 6% of the H. pylori-positive healthy controls. The IL-8 heterozygote mutant variant was detected with a significantly higher frequency among the DU patients and those with gastritis than among the H. pylori-positive controls. However, no significant correlation concerning the frequency of the TLR4 gene polymorphism could be revealed between any group of patients and the controls.


CONCLUSIONS
E266K CARD4/NOD1, but not the TLR4 gene polymorphism increases the risk of peptic ulceration in H. pylori-positive patients. The -251 IL-8 polymorphism was significantly associated with either gastritis or DU in H. pylori-infected subjects. Host factors including intracellular pathogen receptors and IL-8 production play an important role in H. pylori-induced gastric mucosal damage.
Hofner
Peter
P
Department of Medical Microbiology and Immunobiology, University of Szeged, Szeged, Hungary.
Gyulai
Zsofia
Z
Kiss
Zsuzsanna F
ZF
Tiszai
Andrea
A
Tiszlavicz
László
L
Tóth
Gábor
G
Szõke
Dominika
D
Molnár
Béla
B
Lonovics
János
J
Tulassay
Zsolt
Z
Mándi
Yvette
Y
D016022:Case-Control Studies; D004381:Duodenal Ulcer / Q000235:genetics* / Q000382:microbiology; D005756:Gastritis / Q000235:genetics* / Q000382:microbiology; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000235:genetics*; D016480:Helicobacter pylori / Q000472:pathogenicity; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics*; D011110:Polymorphism, Genetic; D051197:Toll-Like Receptor 4 / Q000235:genetics*
D016209:Interleukin-8; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4