30 The frequency of the 842G and 50T polymorphism in Western populations is 10.5% and 8.6% respectively, but no variants have been detected in the Japanese population.31,32 The previous data show an inverse association between the prevalence of A-842G/C50T polymorphism and bleeding peptic ulcer disease, but lack

statistical significance.33 In contrast, a recent Japanese study indicated a possible association of COX-1 T-1676C polymorphism with NSAID-induced peptic ulcer.34 However, there are no data Acalabrutinib supporting a significant association among aspirin users.31 The major enzymes involved in the metabolism of aspirin are known to be polymorphic and comprise cytochrome p450 2C9 (CYP2C9) for hydroxylation of aspirin and UDP-glucuronosyltransferase 1A6 (UGT1A6) for glucuronidation. There are known variant alleles for UGT1A6 and CYP2C9, which STA-9090 in vivo result in a change in amino acids and reduced enzyme activity compared with the wild-type allele.35,36 A previous report described a modulation of the protective effect of aspirin on colon adenoma risk by UGT1A6 (T181A and R184S) and to a lesser extent by CYP2C9, indicating that the

chemopreventive effectiveness of aspirin can be modulated by the genotype of the metabolizing enzymes.37 Two published studies evaluating CYP2C9 polymorphisms in patients with non-aspirin NSAID-related GI bleeding report a significantly increased risk of bleeding in patients carrying the CYP2C9 variants.37,38 In contrast, another study from the Netherlands found no association between CYP2C9 genotype and development of serious NSAID-related ulcers. The frequencies of these gene variants in Japanese are less selleck chemicals than in Western populations,32,39–42 and there was no previous clinical data indicating a significant relation between polymorphisms of UGT1A6 or CYP2C9 and aspirin-induced peptic ulcer or bleeding.43 Interleukin-1β (IL-1β) is important in initiating and amplifying the inflammatory responses to H. pylori infection, and also a potent

inhibitor of gastric acid secretion.44 The IL-1β gene is highly polymorphic and there are transitions of C to T and T to C at positions −511 and −31 of IL-1β. The IL-1β-511 T/T and C/T genotypes are associated with increased IL-1β production, whereas the IL-1β-511 C/C genotype is not.45 Increased production of IL-1β in the gastric mucosa is thought to result in enhanced suppression of gastric acid secretion, as well as enhanced inflammation. The IL-1β-511 T allele is associated with increased risk of gastric cancer development linked with severe corpus atrophy in Western populations,46 and it has been reported that the IL-1β-511 T/T genotype and IL-1RN allele 2 play a protective role against duodenal ulcer in the Japanese population.45,47 Among Japanese LDA users, carriage of the IL-1β-511 T allele was significantly associated with peptic ulcer (OR 0.46, 95% CI 0.22–0.96 in all subjects and OR 0.27, 95% CI 0.10–0.74 in the H. pylori-positive subjects).