NOD1 gene E266K polymorphism is associated with disease susceptibility but not with disease phenotype or NOD2/CARD15 in Hungarian patients with Crohn's disease

Molnár, Tamás; Höfner, P.; Nagy, Ferenc; Lakatos, Péter L.; Fischer, Simon; Lakatos, László; Kovács, Ágota; Altorjay, István; Papp, Mária; Palatka, Károly; Demeter, Pál; Tulassay, Zsolt; Nyári, Tibor; Miheller, Pál; Papp, J.; Mándi, Yvette; Lonovics, J.

doi:10.1016/j.dld.2007.09.003

Cited by 33 publications

(27 citation statements)

References 25 publications

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“…It is generally accepted that H. Pylori is involved in gastric carcinogenesis, as proposed by Correa's model of the development of gastric carcinoma from normal gastric tissue through superficial gastritis, multifocal atrophic gastritis, intestinal metaplasia and dysplasia to carcinoma [34][35][36][37]. The enhanced mucosal inflammation had been suggested to play an important role in H. Pylori induced pathogenesis [38,39].…”

Section: Discussionmentioning

confidence: 98%

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The significance of E266K polymorphism in the NOD1 gene on Helicobacter Pylori infection: an effective force on pathogenesis?

et al. 2009

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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.

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Section: Discussionmentioning

confidence: 98%

“…The 796G to A transition (E266K) in exon 3 was analyzed by PCR restriction fragment length polymorphism (PCR-RFLP) [34]. The reaction mixture of 50 ll contained 100 ng of genomic DNA, 20 pmol of each primer (sence: (Fig.…”

Section: Nod1 Polymorphism Genotypingmentioning

confidence: 99%

The significance of E266K polymorphism in the NOD1 gene on Helicobacter Pylori infection: an effective force on pathogenesis?

et al. 2009

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“…This suggests that loss of specific local inflammatory responses results in more severe, uncontrolled inflammation. This might partially explain the association of the human NOD1 locus with Crohn's disease in some populations (18)(19)(20). Whereas the epithelial permeability is not regulated by Nod1 after C. difficile infection, Nod1 deficiency affects epithelial permeability through the promotion of intestinal epithelial cell survival during dextran sulfate sodium-induced colitis (21).…”

Section: Discussionmentioning

confidence: 99%

Nucleotide-Binding Oligomerization Domain 1 Mediates Recognition of Clostridium difficile and Induces Neutrophil Recruitment and Protection against the Pathogen

Hasegawa

Yamazaki

Kamada

et al. 2011

The Journal of Immunology

157

199

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Clostridium difficile is a Gram-positive obligate anaerobic pathogen that causes pseudomembranous colitis in antibiotics-treated individuals. However, host immune protective mechanisms against C. difficile are largely unknown. In this study, we show that C. difficile possesses potent stimulatory activity for nucleotide-binding oligomerization domain 1 (Nod1), an intracellular pattern recognition molecule that senses bacterial peptidoglycan-related molecules. Nod1−/−, but not Nod2−/−, mice exhibited increased lethality in response to C. difficile intestinal infection despite comparable levels of intestinal damage and epithelial permeability in Nod1−/− and control mice. The enhanced lethality was accompanied by impaired C. difficile clearance, increased bacterial translocation, and elevated levels of endotoxin and IL-1β in the serum of Nod1−/− mice. Histological and flow cytometric analyses revealed that Nod1−/− mice had defective recruitment of neutrophils, but not macrophages, to the intestine after C. difficile infection. The reduced recruitment of neutrophils correlated with impaired production of CXCL1, but not CCL2, XCL1, and other cytokines/chemokines, in infected Nod1−/− mice. The influx of neutrophils also was reduced when C. difficile was administered i.p., suggesting that Nod1 directly recognizes C. difficile to induce the recruitment of neutrophils to the infected site. These results indicate that Nod1 regulates host susceptibility to C. difficile and suggest that Nod1-mediated neutrophil recruitment is an important immune response against the enteric pathogen.

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“…For example, 29.6% of DEFEB1 20A carriers were antiglycan positive compared to 46% positivity in non-carriers (P < 0.038). However, no association of antiglycan positivity was found with either DEFEB1 G52A variant or DLG5 (R30Q), although both were shown to be associated with increased risk for CD [53,54] . Furthermore, in contrast to other reports [32,51] , no gene dosage effect was observed on any of the antiglycan antibodies.…”

Section: "New" Serological Ibd Biomarkersmentioning

confidence: 73%

New serological biomarkers of inflammatory bowel disease

Li¹,

Conklin²,

Alex³

2008

WJG

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NOD1 gene E266K polymorphism is associated with disease susceptibility but not with disease phenotype or NOD2/CARD15 in Hungarian patients with Crohn's disease

Cited by 33 publications

References 25 publications

The significance of E266K polymorphism in the NOD1 gene on Helicobacter Pylori infection: an effective force on pathogenesis?

The significance of E266K polymorphism in the NOD1 gene on Helicobacter Pylori infection: an effective force on pathogenesis?

Nucleotide-Binding Oligomerization Domain 1 Mediates Recognition of Clostridium difficile and Induces Neutrophil Recruitment and Protection against the Pathogen

New serological biomarkers of inflammatory bowel disease

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