CYP2C19*17 Gain‐of‐Function Polymorphism Is Associated With Peptic Ulcer Disease. Issue 2 (26th October 2012)

• Record Type: Journal Article
• Authors: Musumba, C O; Jorgensen, A; Sutton, L; Van Eker, D; Zhang, E; O'Hara, N; Carr, D F; Pritchard, D M; Pirmohamed, M
• Is Part Of: Clinical pharmacology & therapeutics. Volume 93:Issue 2(2013)
• Page Start: 195
• Page End: 203
• Publication Date: 2012-10-26
• Subjects: Pharmacology -- Periodicals; Therapeutics -- Periodicals; 615.5
• DOI: 10.1038/clpt.2012.215
• Languages: English
• ISSNs: 0009-9236

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Single‐nucleotide polymorphisms (SNPs) in the <italic>CYP2C</italic> 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 <italic>CYP2C</italic> family of genes—<italic>CYP2C8*3</italic> (rs11572080 and rs10509681), <italic>CYP2C8*4</italic>, <italic>CYP2C9*2</italic>, <italic>CYP2C9*3</italic>, <italic>CYP2C19*2</italic>, <italic>CYP2C19*3</italic>, and <italic>CYP2C19*17</italic>—are associated with PUD in 1, 239 Caucasian patients. Logistic regression analysis showed that only <italic>CYP2C19*17</italic> was associated with PUD (odds ratio additive model: 1.47 (95% confidence interval (CI) 1.12 to 1.92); <italic>P</italic> = 0.005; R<sup>2</sup> 16%), but not UGIB, independent of NSAID use or <italic>Helicobacter pylori</italic> infection. PUD distribution varied (<italic>P</italic> = 0.024) according to <italic>CYP2C19*17</italic> genotype: <italic>*1/*1</italic>, 490 (64.3%); <italic>*1/*17</italic>, 304 (71.7%); and <italic>*17/*17</italic>, 31 (73.8%). <italic>CYP2C19*17</italic>, a gain‐of‐function polymorphism, is associated with PUD irrespective of etiology.</p> <p> <italic>Clinical Pharmacology & Therapeutics</italic> (2013); <bold>93</bold> 2, 195–203. doi:<ext-link ext-link-type="doi" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">10.1038/clpt.2012.215</ext-link></p> </abstract>