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CYP2C19*17 gain-of-function polymorphism is associated with peptic ulcer disease.
C O Musumba1, A Jorgensen, L Sutton
1Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
Clinical Pharmacology and Therapeutics
|December 27, 2012
Summary
Single-nucleotide polymorphisms (SNPs) in the CYP2C gene cluster, specifically CYP2C19*17, are linked to peptic ulcer disease (PUD). This gain-of-function polymorphism increases PUD risk, independent of NSAID use or H. pylori infection.
Area of Science:
- Pharmacogenomics
- Gastroenterology
- Genetics
Background:
- Single-nucleotide polymorphisms (SNPs) in the CYP2C gene cluster are studied for their role in nonsteroidal anti-inflammatory drug (NSAID)-induced peptic ulcer disease (PUD) and upper gastrointestinal bleeding (UGIB).
- Previous studies yielded inconclusive results due to varied designs, limited genotyping, and small sample sizes.
Purpose of the Study:
- To investigate the association between eight functional SNPs in the CYP2C gene family and PUD in a Caucasian patient cohort.
- To determine if these SNPs are associated with NSAID-induced PUD or UGIB.
Main Methods:
- Genotyping of eight functional SNPs: CYP2C8*3 (rs11572080 and rs10509681), CYP2C8*4, CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, and CYP2C19*17.
- Logistic regression analysis was performed on data from 1,239 Caucasian patients.
- Analysis considered NSAID use and Helicobacter pylori infection as potential confounders.
Main Results:
- The CYP2C19*17 polymorphism was significantly associated with PUD (OR 1.47, P=0.005), but not with UGIB.
- This association remained independent of NSAID use and H. pylori infection.
- PUD prevalence varied across CYP2C19*17 genotypes: 64.3% (*1/*1), 71.7% (*1/*17), and 73.8% (*17/*17).
Conclusions:
- CYP2C19*17, a gain-of-function polymorphism, is associated with an increased risk of peptic ulcer disease.
- This genetic association with PUD is independent of common etiological factors like NSAID use and H. pylori infection.
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