CYP2C1917 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 d...

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Published in:Clinical pharmacology and therapeutics 2013-02, Vol.93 (2), p.195-203
Main Authors: Musumba, C O, Jorgensen, A, Sutton, L, Van Eker, D, Zhang, E, O'Hara, N, Carr, D F, Pritchard, D M, Pirmohamed, M
Format: Article
Language:English
Subjects:
Anti-Inflammatory Agents, Non-Steroidal - adverse effects
Aryl Hydrocarbon Hydroxylases - genetics
Biological and medical sciences
Case-Control Studies
Cytochrome P-450 CYP2C19
European Continental Ancestry Group
Female
Gastroenterology. Liver. Pancreas. Abdomen
Gastrointestinal Hemorrhage - chemically induced
Gastrointestinal Hemorrhage - genetics
Helicobacter Infections - complications
Humans
Logistic Models
Male
Medical sciences
Odds Ratio
Other diseases. Semiology
Peptic Ulcer - chemically induced
Peptic Ulcer - genetics
Pharmacology. Drug treatments
Polymorphism, Single Nucleotide
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
United Kingdom
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Summary: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; R2 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. Clinical Pharmacology & Therapeutics (2013); 93 2, 195–203. doi:10.1038/clpt.2012.215
ISSN:0009-9236
1532-6535
DOI:10.1038/clpt.2012.215