Association between promoter polymorphisms of nuclear factor-erythroid 2-related factor 2 gene and peptic ulcer diseases.
Transcription factor Nrf2 regulates the expression of detoxifying and antioxidant genes. Three promoter polymorphisms of this gene have been identified. We attempted to clarify the association of these polymorphisms with the development of peptic ulcer diseases. The study was performed with 384 stocked DNAs obtained from subjects with no evidence of gastric malignancy. In all 384 DNAs, 77 and 48 were obtained from gastric and duodenal ulcer patients, respectively. By an unadjusted analysis, infection with Helicobacter pylori (H. pylori), male gender and the -686/-684 G/G carrier (OR, 2.52; 95% CI, 1.19-5.45; p=0.016) were associated with a significantly increased risk for developing gastric ulcer, whereas the -686/-684 A/G homozygote was linked to a significantly reduced risk for developing gastric ulcer (OR, 0.26; 95% CI, 0.099-0.67; p=0.0055). On the other hand, infection with H. pylori and male gender were significantly associated with the development of duodenal ulcer, whereas Nrf2 promoter polymorphisms were not. By the analysis, after adjustment for age, gender, non-steroidal anti-inflammatory drug/aspirin use and H. pylori infection status, the -686/-684 A/G homozygote was associated with a significantly reduced risk for gastric ulcer (OR, 0.25; 95% CI, 0.088-0.73; p=0.011). Our results suggest that promoter polymorphisms of the Nrf2 gene are associated with the susceptibility to gastric ulcer.
Arisawa
Tomiyasu
T
Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake 470-1192, Japan. tarisawa@fujita-hu.ac.jp
Tahara
Tomomitsu
T
Shibata
Tomoyuki
T
Nagasaka
Mitsuo
M
Nakamura
Masakatsu
M
Kamiya
Yoshio
Y
Fujita
Hiroshi
H
Yoshioka
Daisuke
D
Arima
Yuko
Y
Okubo
Masaaki
M
Hirata
Ichiro
I
Nakano
Hiroshi
H
D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D010437:Peptic Ulcer / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011897:Random Allocation; D012307:Risk Factors
D051267:NF-E2-Related Factor 2