16,17 The two variant alleles, designated as CYP2C9*2 and CYP2C9*3, consist of single-nucleotide substitutions that cause the amino acid changes R144C and I359L, respectively. Both variant alleles lead to decreased enzyme activity on CYP2C9 substrates compared with the wild-type allele. Martinez LY2157299 et al.17 demonstrated that

the frequency of CYP2C9 variant alleles was increased in patients with acute bleeding (OR = 1.64, 95% CI = 1.05–2.58; P = 0.02). In another case–control study of 26 patients with NSAID-related upper GI bleeding and 52 controls, setting the CYP2C9*1/*1 wild type as reference, there were significantly higher frequencies of CYP2C9*1/*3 (34.6% vs 5.8%; P < 0.001; MAPK inhibitor OR = 12.9, 95% CI = 2.9–58) and CYP2C9*1/*2 (26.9% vs 15.4%; P = 0.036; OR = 3.8, 95% CI = 1.1–13) identified in the patients with

bleeding compared to control patients. The presence of the CYP2C9*3 allele was associated with a significantly high risk of bleeding (adjusted OR = 7.3, 95% CI = 2.1–26).16 In contrast, another study from the Netherlands found no association between the CYP2C9 genotype and development of serious NSAID-related ulcers. There are no previous clinical data indicating a significant relationship between polymorphisms of UGT1A6 or CYP2C9 and aspirin-induced peptic ulcer.18 The frequencies of these gene variants in Japanese are less than those in Western populations.12,19–22 In our recent study of low-dose aspirin users, which included 40 patients with peptic ulcer, there was no significant association between these gene variants and peptic ulcer;12,19 however, we could not evaluate bleeding risk because of the small number of subjects, and the number of patients with peptic ulcer was also small. A further large-scale clinical study is required to investigate selleck the association between aspirin-induced ulcer and the genotype of enzymes metabolizing aspirin, especially CYP2C9. Helicobacter pylori and NSAIDs are now recognized as

the two most important etiological factors in peptic ulcer and its complications;23–25 however, the studies report conflicting findings that H. pylori infection increases, has no effect on, or even decreases the risk of NSAID-related ulcers. A meta-analysis of randomized trials (five studies and 939 patients) evaluating whether eradication of H. pylori prevented peptic ulcer in NSAID users suggested that H. pylori eradication reduced the incidence of peptic ulcer in the NSAID-naive patients (OR = 0.26, 95% CI = 0.14–0.49), but not in previously treated patients (OR = 0.95, 95% CI = 0.53–1.72).25 The fact that eradication appears to be effective when performed in NSAID-naive patients is consistent with H. pylori infection having an enhancing effect on NSAID gastrotoxicity or NSAIDs exacerbating H. pylori ulcer or H. pylori ulcerogenesis. We have previously found no association between H.