Inducible nitric oxide synthase polymorphism is associated with the increased risk of differentiated gastric cancer in a Japanese population

AIM： To examine the association of inducible nitric oxide synthase （iNOS） C150T polymorphism with gastric cancer, as well as with gastric atrophy and H pylori seropositivity.METHODS： A single nucleotide polymorphism of iNOS CtSOT was examined for 454 Japanese health checkup examinees （126 males and 328 females） aged 35 to 85 years without a history of cancer and 202 gastric cancer patients （134 males and 68 females） aged 33 to 94 years with pathologically confirmed diagnosis of gastric adenocarcinoma.RESULTS： The iNOS C150T polymorphism was not associated with gastric atrophy or with H pylori seropositivity. The odds ratio （OR） of the C/T ＋T/T for gastric cancer was increased without statistical significance （OR=1.19, 95% confidence interval （CI）： 0.68-2.08）. In the differentiated subgroup （n = 113）, however, the OR of the C/T genotvpe for gastric cancer was significant （OR = 2.02, 95% CI： 1.04-3.92） relative to the C/C genotype. In addition, considering the location of gastric cancer （n = 105）, there were significant differences between the controls and non-cardia group with the ORof 2.13 （95% CI： 1.08-4.18） for C/T and 1.94 （95% CI： 1.00-3.78） for C/T ＋ T/T.CONCLUSION： The iNOS C150T polymorphism is associated with the risk of H pylori-related gastric cancer in a Japanese population. This polymorphism may play an important role in increasing the risk of gastric cancer in Asian countires with the highest rates of gastric cancer.

Expression of differential nitric oxide synthase isoforms in human gastric mucosa infected with Helicobacter pylori

Objective: To study the relationship between nitric oxide synthase (NOS) expression in human gastric mucosa and Helicobacter pylori (H.pylori) infection. Methods: Gastric mucosa samples were obtained from antrum of 33 patients received gastroendoscopy. H.pylori infection was confirmed by Giems staining and bacteria culture under microaerophilic conditions. Expression of iNOS, eNOS and nitrotyrosine were detected by immunohistochemistry. Results: (1) The positive rate of H. pylori infection was 66.7%(22/33). (2) iNOS positive staining in inflammatory cells was detected in 77.3%(17/22) of samples with H.pylori and 27.3%(3/11) without H.pylori infection (P<0.01). (3) eNOS expression in inflammatory cells was found in 77.3%(17/22) of samples with H. pylori and 18.2%(2/11) without H.pylori infection (P<0.01). (4) Nitrotyrosine expression in inflammatory cells was observed in 59.1%(13/22) of samples with H. pylori and 54.5%(6/11) without H. pylori infection (P>0.05). (5) Moderate and severe infiltrations of inflammatory cells were found in 86.4%(19/22) of gastric biopsies with H. pylori and 9.1%(1/11) of samples without H. pylori infection (P<0.01). Conclusion: H.pylori infection might promote infiltration of mononuclear cells and macrophages in gastric mucosa and induce iNOS expression in these cells. The accumulated nitric oxide in local area may result in gastric mucosa damage.

Response of blood endothelin-1 and nitric oxide activity in duodenal ulcer patients undergoing Helicobacter pylori eradication

AIM: To investigate the effect of Helicobacter pylori eradication on endothelin-1 (ET-1) and nitric oxide (NO) in duodenal ulcer (DU) patients. METHODS: Sixty-six Hpylori-infected active DU patients were consecutively enrolled to receive one-week triple therapy (rabeprazole, amoxicillin and metronidazole) and then one-month rabeprazole therapy. They were asked back to determine ulcer and Hpylori status using endoscopy one month later. Thirty-seven healthy controls (H pylori +/-:17/20) were enrolled for comparison. Blood samples were collected in each visit to measure plasma ET-1 and nitrate/nitrite levels using an enzyme immunoassay kit. RESULTS: Sixty DU patients finished trial per protocol. The ulcer healing and Hpylori-eradication rates were 86.7% and 83.3%, respectively. Plasma ET-1 level in DU patients was higher than that of Hpylori-negative and positive controls (3.59±0.96 vs0.89±0.54 vs0.3±0.2 pg/mL,P<0.01), while nitrate/nitrite levels among them were also significantly different (8.55±0.71 vs5.27±0.68 vs 6.39±0.92 μmol/L, P<0.05). H pylori eradication diminished ET-1 levels (3.64±0.55 vs2.64±0.55 pg/mL, P<0.01) but elevated nitrate/ nitrite level (8.16±0.84 vs11.41±1.42 umol/L,P<0.05). CONCLUSION: Both plasma ET-1 and nitrate/nitrite levels increase in active DU patients. After an effective H pylori eradication, DU healing is associated with diminished blood ET-1 level and elevated nitrate/nitrite level.