CYP2C19*17 gain-of-function polymorphism is associated with peptic ulcer disease.

Single-nucleotide polymorphisms (SNPs) in the CYP2C gene cluster have been extensively investigated as predisposing factors for nonsteroidal anti-inflammatory drug (NSAID)-induced peptic ulcer disease (PUD) or upper gastrointestinal bleeding (UGIB). However, results have been inconclusive owing to different study designs, limited genotyping strategies, and small sample sizes. We investigated whether eight functional SNPs in the CYP2C family of genes--CYP2C8*3 (rs11572080 and rs10509681), CYP2C8*4, CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, and CYP2C19*17--are associated with PUD in 1,239 Caucasian patients. Logistic regression analysis showed that only CYP2C19*17 was associated with PUD (odds ratio additive model: 1.47 (95% confidence interval (CI) 1.12 to 1.92); P = 0.005; R(2) 16%), but not UGIB, independent of NSAID use or Helicobacter pylori infection. PUD distribution varied (P = 0.024) according to CYP2C19*17 genotype: *1/*1, 490 (64.3%); *1/*17, 304 (71.7%); and *17/*17, 31 (73.8%). CYP2C19*17, a gain-of-function polymorphism, is associated with PUD irrespective of etiology.

The relative contribution of NSAIDs and Helicobacter pylori to the aetiology of endoscopically-diagnosed peptic ulcer disease: observations from a tertiary referral hospital in the UK between 2005 and 2010.

BACKGROUND: Recent data from Western countries indicate that the aetiology of peptic ulcer disease (PUD) is changing as the prevalence of Helicobacter pylori is decreasing while the use of low-dose aspirin (LDA, ≤325 mg/day) is increasing. AIM: To investigate the changing aetiology and demographics of PUD in a well-characterised patient cohort at a large tertiary hospital in the UK between July 2005 and June 2010. METHODS: Patients diagnosed with PUD following endoscopy were categorised as non-steroidal anti-inflammatory drug (NSAID)-users or non-users, and their H. pylori status determined. Comparisons between NSAID-users and non-users, and between non-aspirin NSAID-users and LDA-users were summarised using counts and corresponding percentages (for categorical variables) and means and standard deviations (for continuous variables). RESULTS: Overall, 386 patients were enrolled; 57% used NSAIDs (51% LDA only) and 43% were non-users. 57% of the whole cohort was H. pylori-positive (including 66% with duodenal ulcers and 47% with gastric ulcers). Compared with non-users, NSAID-users were older (mean age 68 vs. 61 years) and fewer were H. pylori-positive (52% vs. 63%). LDA-users were older (mean age 71 vs. 62 years) and more likely to be H. pylori-positive (61% vs. 41%) than those using non-aspirin NSAIDs. Twelve per cent of the patients were neither using NSAIDs nor were H. pylori-positive. CONCLUSIONS: The NSAIDs, particularly LDA, were most commonly associated with PUD in this cohort. Our findings are compatible with the decline in the prevalence of H. pylori-positive PUD and increase in non-NSAID, non-H. pylori PUD previously reported.