title: The significance of E266K polymorphism in the NOD1 gene on Helicobacter pylori infection: an effective force on pathogenesis?
abstract: The severity of Helicobacter pylori-related diseases varies greatly among infected individuals and seems to be influenced by both host and bacterial factors. Infection with a cytotoxin-associated gene pathogenicity island (Cag PAI)-positive H. Pylori strain causes a higher grade of gastric mucosal inflammation than an infection caused by a negative strain. Furthermore, such an infection is associated with severe atrophic gastritis and gastric adenocarcinoma. NOD1 protein is a cytosolic pattern recognition receptor that responds to peptidoglycan delivered by H. Pylori cag pathogenicity island. The aim of this study is to investigate whether the presence of the NOD1 G796A polymorphism has any influence on the clinical outcomes of Cag PAI-positive H. Pylori. Both Helicobacter pylori and CagA-positive 150 patients were considered eligible for the study. In this selected group, NOD1 G796A was detected by using polymerase chain reaction/restriction fragment length polymorphism. Activity and severity of gastritis, atrophy, intestinal metaplasia and Helicobacter pylori density were assessed in body and antral biopsies. Also post-therapy controls for predicting Helicobacter pylori persistence were done. The correlations of these parameters were determined by SPSS 15 packet program for statistical analysis. Of the 150 CagA-positive patients, 57 had (38%) heterozygote (GA), and 29 had (19.3%) homozygote (AA) mutant variants of NOD1. The other 64 patients had (42.7%) wild-type DNA(GG). NOD1 796A allele carriers had higher risk for antral atrophy (OR = 13.35, 95% CI = 5.12-34.82) and antral intestinal metaplasia (OR = 2.71, 95% CI = 1.26-5.80). Carriage of the single nucleotide polymorphism of NOD1 G796A proved to be a significant risk factor for the Helicobacter pylori therapy failure (OR = 4.62, 95% CI = 1.67-12.79). Our results suggest that carriage of the NOD1 G796A mutation increases the susceptibility of gastric epithelial cells for intestinal metaplasia and atrophy when infected by CagA-positive Helicobacter pylori strains. Additionally, it increases the ratio of eradication failure.
authors.affiliation: Faculty of Medicine, Department of Gastroenterology, Cukurova University, Yuregir, Adana 01330, Turkey. banu97@superonline.com
authors.forename: Banu
authors.initials: B
authors.lastname: Kara
authors.forename: Hikmet
authors.initials: H
authors.lastname: Akkiz
authors.forename: Figen
authors.initials: F
authors.lastname: Doran
authors.forename: Suleyman
authors.initials: S
authors.lastname: Bayram
authors.forename: Eren
authors.initials: E
authors.lastname: Erken
authors.forename: Yuksel
authors.initials: Y
authors.lastname: Gumurdullu
authors.forename: Macit
authors.initials: M
authors.lastname: Sandikci
mesh_terms: D000328:Adult; D015169:Colony Count, Microbial; D005260:Female; D005757:Gastritis, Atrophic / Q000473:pathology; D016481:Helicobacter Infections / Q000235:genetics* / Q000473:pathology*; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D020125:Mutation, Missense; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012720:Severity of Illness Index; D013270:Stomach / Q000382:microbiology / Q000473:pathology
chemical_list: C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein