Association between genetic polymorphisms in the cyclooxygenase-1 gene promoter and peptic ulcers in Japan

Tomiyasu Arisawa, Tomomitsu Tahara, Tomoyuki Shibata, Mitsuo Nagasaka, Masakatsu Nakamura, Yoshio Kamiya, Hiroshi Fujita, Masahiko Nakamura, Daisuke Yoshioka, Yuko Arima, Masaaki Okubo, Ichiro Hirata, Hiroshi Nakano

Research output: Contribution to journalArticle

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Abstract

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 antiinflammatory 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.

Original languageEnglish
Pages (from-to)373-378
Number of pages6
JournalInternational Journal of Molecular Medicine
Volume20
Issue number3
Publication statusPublished - 01-09-2007

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Cyclooxygenase 1
Genetic Polymorphisms
Stomach Ulcer
Peptic Ulcer
Japan
Helicobacter Infections
Alleles
Helicobacter pylori
Non-Steroidal Anti-Inflammatory Agents
Duodenal Ulcer
Genes
Stomach
Single-Stranded Conformational Polymorphism
Gastritis
Gastric Mucosa
Drug Users
Population
Ulcer
Prostaglandins
Atrophy

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Arisawa, T., Tahara, T., Shibata, T., Nagasaka, M., Nakamura, M., Kamiya, Y., ... Nakano, H. (2007). Association between genetic polymorphisms in the cyclooxygenase-1 gene promoter and peptic ulcers in Japan. International Journal of Molecular Medicine, 20(3), 373-378.
Arisawa, Tomiyasu ; Tahara, Tomomitsu ; Shibata, Tomoyuki ; Nagasaka, Mitsuo ; Nakamura, Masakatsu ; Kamiya, Yoshio ; Fujita, Hiroshi ; Nakamura, Masahiko ; Yoshioka, Daisuke ; Arima, Yuko ; Okubo, Masaaki ; Hirata, Ichiro ; Nakano, Hiroshi. / Association between genetic polymorphisms in the cyclooxygenase-1 gene promoter and peptic ulcers in Japan. In: International Journal of Molecular Medicine. 2007 ; Vol. 20, No. 3. pp. 373-378.
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abstract = "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 antiinflammatory 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.",
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Arisawa, T, Tahara, T, Shibata, T, Nagasaka, M, Nakamura, M, Kamiya, Y, Fujita, H, Nakamura, M, Yoshioka, D, Arima, Y, Okubo, M, Hirata, I & Nakano, H 2007, 'Association between genetic polymorphisms in the cyclooxygenase-1 gene promoter and peptic ulcers in Japan', International Journal of Molecular Medicine, vol. 20, no. 3, pp. 373-378.

Association between genetic polymorphisms in the cyclooxygenase-1 gene promoter and peptic ulcers in Japan. / Arisawa, Tomiyasu; Tahara, Tomomitsu; Shibata, Tomoyuki; Nagasaka, Mitsuo; Nakamura, Masakatsu; Kamiya, Yoshio; Fujita, Hiroshi; Nakamura, Masahiko; Yoshioka, Daisuke; Arima, Yuko; Okubo, Masaaki; Hirata, Ichiro; Nakano, Hiroshi.

In: International Journal of Molecular Medicine, Vol. 20, No. 3, 01.09.2007, p. 373-378.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association between genetic polymorphisms in the cyclooxygenase-1 gene promoter and peptic ulcers in Japan

AU - Arisawa, Tomiyasu

AU - Tahara, Tomomitsu

AU - Shibata, Tomoyuki

AU - Nagasaka, Mitsuo

AU - Nakamura, Masakatsu

AU - Kamiya, Yoshio

AU - Fujita, Hiroshi

AU - Nakamura, Masahiko

AU - Yoshioka, Daisuke

AU - Arima, Yuko

AU - Okubo, Masaaki

AU - Hirata, Ichiro

AU - Nakano, Hiroshi

PY - 2007/9/1

Y1 - 2007/9/1

N2 - 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 antiinflammatory 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.

AB - 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 antiinflammatory 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.

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