title: The relationship between Helicobacter pylori infection and promoter polymorphism of the Nrf2 gene in chronic gastritis.
abstract: The transcription factor Nrf2 regulates the expression of detoxifying and antioxidant genes. Three polymorphisms of the Nrf2 gene have been reported. We attempted to clarify the relationship between Nrf2 gene polymorphism and chronic gastritis in a Japanese population. The study was performed in 159 patients with no evidence of gastric malignancy on upper gastrointestinal endoscopy (mean age, 62.03 years; male:female ratio, 102:57; peptic ulcer diseases in 69 patients, and Helicobacter pylori (H. pylori) positivity in 73.0%). We employed the PCR-SSCP method to detect gene polymorphisms using DNA extracted from peripheral blood cells or from antral biopsy specimens obtained by endoscopy. The severity of the histological chronic gastritis in antral biopsy specimens was classified according to the updated Sydney system. Although the frequencies of the SNP(-686) and SNP(-650) A alleles were decreased in subjects with peptic ulcers or severe mucosal atrophy, no significant differences were seen. However, the number of -686 G alleles was correlated with both neutrophil activity and mononuclear cell infiltration (p=0.036 and p=0.010, respectively), while the -650 C/C genotype was an independent risk factor for mononuclear cell infiltration (p=0.021 by ANOVA). In addition, both the number of -686 G alleles and the -650 C/C genotype showed an interaction with H. pylori infection to promote the infiltration of mononuclear cells (p=0.037 by ANCOVA and p=0.041 by ANOVA, respectively). Nrf2 promoter polymorphisms are significantly associated with the development of gastric mucosal inflammation, either independently or by interacting with H. pylori infection.
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Dengakugakubo, Toyoake 470-1192, Japan. tarisawa@fujita-hu.ac.jp
authors.forename: Tomiyasu
authors.initials: T
authors.lastname: Arisawa
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Tahara
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shibata
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Nagasaka
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kamiya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujita
authors.forename: Shin
authors.initials: S
authors.lastname: Hasegawa
authors.forename: Tamaki
authors.initials: T
authors.lastname: Takagi
authors.forename: Fang-Yu
authors.initials: FY
authors.lastname: Wang
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hirata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakano
mesh_terms: D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology; D005756:Gastritis / Q000209:etiology* / Q000235:genetics; D005787:Gene Frequency; D016481:Helicobacter Infections / Q000150:complications* / Q000235:genetics; D006801:Humans; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human