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

Abstract

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.

The preventive factors for aspirin-induced peptic ulcer: aspirin ulcer and corpus atrophy

“…We detected UGT1A6 and CYP2C9 gene variants in 43.5 and 3.0% of patients, respectively. These frequencies were similar to those in previous Japanese studies [23][24][25][26][27][28], which were lower compared with those in Western populations [20]. We found no significant association between these gene variants and peptic ulcer among patients taking low dose aspirin.…”

“…The frequencies of the genotypes were almost the same as those of the data published previously by other Japanese investigators [3,15,23,24].…”

“…There were no significant differences between the ulcer group and the non-ulcer group among either all subjects or in the H. pylori-positive subgroup. A-842G/C50T COX polymorphism was not detected in any of the 232 subjects as noted in a previous Japanese report [24]. The carriage of the COX-1-1676 C allele was not associated with peptic ulcer in the patients taking aspirin.…”

“…The previous data on genetic diversity of COX-1 in Western populations showed an inverse association between the prevalence of A-842G/C50T polymorphism and bleeding peptic ulcer disease, but the data lacked statistical significance [21]. In contrast, a recent Japanese study indicated an association of T-1676C polypmorphism with NSAID-induced ulcer [24]. In their results, the frequency of -1676 T carriers was significantly higher in patients with ulcer diseases than in non-ulcer subjects and the number of -1676T alleles was a significant risk factor for developing ulcer diseases in NSAID users.…”

AGT A-20C (rs5050) gene polymorphism and ulcer occurrence in patients treated with low-dose aspirin: a case-control study / Polimorfismul AGT A-20C și ulcerele gastro-duodenale la pacienții sub tratament cu aspirină în doze antiagregante: studiu caz-control

“…Cytochrome P450 2C9 (CYP2C9) variants were reported to increase the risk for ulcer bleeding in NSAIDs consumers in several studies [6]. In a Japanese study, a polymorphism of the gene encoding cyclooxygenase (COX-1-1676 T allele) was associated with ulcer in NSAIDs consumers [7], while another study reported the carriage of interleukin-1β (IL-1b-511T) T allele to be associated with an increased risk for ulcer in aspirin consumers [8]. Another Japanese study has recently demonstrated an increased risk for bleeding in LDA consumers harboring the angiotensinogen variant genotype (AGT-20 CC) [9].…”