CYP2C19*17 Gain-of-Function Polymorphism Is Associated With Peptic Ulcer Disease

1] Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK [2] Department of Gastroenterology, University of Liverpool, Liverpool, UK [3] The Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK.
Clinical Pharmacology &#38 Therapeutics (Impact Factor: 7.9). 10/2012; 93(2). DOI: 10.1038/clpt.2012.215
Source: PubMed


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.Clinical Pharmacology & Therapeutics (2012); advance online publication 26 December 2012. doi:10.1038/clpt.2012.215.

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    • "A recent study has linked CYP2C19*2 rs4244285 with the regulation of blood pressure [47]. CYP2C19 may also influence arachidonic acid metabolism predisposing to peptic ulcer disease [48,49] and vascular disease [50]. These functions might also influence the interaction with environmental pathogens although the mechanism by which the resulting selective force might operate and the strength of the selective pressure that would result is not clear. "
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