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.

Markers for Gastric Cancer Premalignant Lesions: Where Do We Go?

“…It has been reported that the NOD1 G796A mutation increases the risk for gastric mucosal atrophy substantially (OR 34.2 for NOD1 796AA, OR 13.35 for NOD1 796GA vs. NOD1 796GG) [57]. …”

Role of NOD1/CARD4 and NOD2/CARD15 gene polymorphisms in cancer etiology

“…Of note, Boffetta et al [114] proposed that sarcoidosis may be associated with increased CRC and kidney cancer risk, and Ji et al [115] suggested that sarcoidosis may be connected with higher risk of squamous cell carcinoma, melanoma, nonthyroid endocrine tumors, non-Hodgkin lymphoma, and leukemia. In addition, a homozygous variant genotype of rs2075820 was associated with elevated risk of peptic ulcer [116], antral atrophy, antral intestinal metaplasia, and eradication failure [117] in HP-positive patients; it also correlated with increased risk of CD [118]. In 2009, Verma et al [119] showed that the A allele of rs72551113 and the G allele of L370R are associated with increased UC risk, whereas the C allele of rs72551107 is connected with lower UC risk.…”

Genetic Factors Involved in the Genesis of Helicobacter Pylori-Induced Gastric Cancer

“…Recent report revealed that the carriage of the NOD1 G796A (E266K) mutation increases the susceptibility for gastric atrophy strikingly: OR = 34.2 in NOD1 796AA and OR = 13.35 in NOD1 796GA compared to subjects with NOD1 796GG (Kara et al, 2010). …”

“…PTPN11 G/A at intron3 intron rs2301756 248 Japanese (Goto, 2006a) GG ,GA :0.70,AA :0.09 *GG (59%),GA (49%),AA (11%) " 979 Japanese (Hishida, 2009a) GG ,GA+AA :0.62 ‡ *GG (22%),GA+AA (15%) ‡ NOD1 G796A Non-synonimous (Glu266Lys) rs2075820 150 Turks (Kara, 2010) GG ,GA : 13.35*,AA :34.2* TLR4 A+896G Non-synonimous (Asp299Gly) rs4986790 103 Caucasians (Hold, 2007) AA ,AG :11.0* AA (36%),AG (87%) § " 717 Venezuelan (Kato, 2007) GlyGly/ AspGly,AspAsp : 1.53 TLR4 G+3725C 3'UTR rs11536889 980 Japanese (Hishida, 2009b) GG,GC+CC:1.33 GG(18%),GC+CC(22%) ‡ CD14 C-159T(C-260T) 5'UTR rs2569190 717 Venezuelan (Kato, 2007) CC,CT+TT :1.06…”