Association between genetic polymorphisms in the cyclooxygenase-1 gene promoter and peptic ulcers in Japan.
Cyclooxygenase-1 (COX-1) has been regarded as a constitutively expressed enzyme that generates prostaglandins for gastrointestinal integrity. We attempted to clarify the association between potentially functional polymorphisms (T-1676C and A-842G/C50T) in the COX-1 gene promoter and gastroduodenal disorders in a Japanese population. The study was performed with 480 stocked DNAs from subjects (gastric ulcers in 93 subjects and duodenal ulcers in 44) with no evidence of gastric malignancy. We employed the PCR-SSCP method to detect gene polymorphisms. The severity of histological chronic gastritis in antral biopsy specimens was classified according to the updated Sydney system. The T-1676C polymorphism was not associated with either gastric mucosal atrophy or infiltration of inflammatory cells into gastric mucosa. In non-NSAID (non-steroidal anti-inflammatory drug) users, male gender and Helicobacter pylori (HP) infection were significantly associated with both gastric and duodenal ulcers, whereas the -1676T allele carrier was significantly associated with only gastric ulcers (OR, 2.86; 95% CI, 1.29-6.34). In NSAID users, the number of -1676T alleles was significantly associated with developing gastroduodenal ulcers (OR, 5.80; 95% CI, 1.59-21.1), whereas male gender and HP infection were not. The -842T/ C50T polymorphism was not detected in any of the 480 Japanese subjects. In conclusion, a carrier of the -1676T allele in the COX-1 gene promoter, as well as HP infection and male gender, seem to be significant risk factors for developing gastric ulcers, and the number of -1676T alleles was also a significant risk factor for the NSAID-induced ulcer, whereas the frequency of the A-842G polymorphism was thought to be very rare in the Japanese population.
Department of Gatroenterology, Fujita Health University School of Medicine, Toyoake 470-1192, Japan. tarisawa@fujita-hu.ac.jp
Tomiyasu
T
Arisawa
Tomomitsu
T
Tahara
Tomoyuki
T
Shibata
Mitsuo
M
Nagasaka
Masakatsu
M
Nakamura
Yoshio
Y
Kamiya
Hiroshi
H
Fujita
Masahiko
M
Nakamura
Daisuke
D
Yoshioka
Yuko
Y
Arima
Masaaki
M
Okubo
Ichiro
I
Hirata
Hiroshi
H
Nakano
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D001284:Atrophy; D001483:Base Sequence; D051545:Cyclooxygenase 1 / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004381:Duodenal Ulcer / Q000201:enzymology / Q000209:etiology / Q000235:genetics / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori / Q000472:pathogenicity; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D010437:Peptic Ulcer / Q000201:enzymology* / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D013276:Stomach Ulcer / Q000201:enzymology / Q000209:etiology / Q000235:genetics / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017931:DNA Primers; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human