Key result
The CYP2C8*3+CYP2C9*2 genotype increased the risk of acute gastrointestinal bleeding in patients receiving CYP2C8/9 substrate NSAIDs (OR 3.7; 95% CI 1.6-8.9; P=0.003).
Why the study?
Do CYP2C8 and CYP2C9 polymorphisms increase the risk of acute gastrointestinal bleeding in patients receiving NSAIDs?
Cross-Sectional (n=311)
Do CYP2C8 and CYP2C9 polymorphisms increase the risk of acute gastrointestinal bleeding in patients receiving NSAIDs?
Odds Ratio: 3.7 (95% CI 1.6–8.9)
Absolute Event Rate: 0.4% vs 0.15%
p-value: p=0.003
The combined presence of CYP2C8*3 and CYP2C9*2 genotypes significantly increases the risk of acute gastrointestinal bleeding in patients taking NSAIDs metabolized by these enzymes.
May warrant caution with CYP2C8/9-substrate NSAIDs in variant carriers but should not change practice; leaves open prospective validation.
OBJECTIVES: To analyze whether gene variants leading to impaired drug metabolism are related with acute gastrointestinal bleeding after nonsteroidal anti-inflammatory drugs (NSAID) use. METHODS: Common CYP2C8 and CYP2C9 polymorphisms were studied in a cross-sectional study, involving 134 NSAID-related bleeding patients and in 177 patients receiving NSAID with no adverse effects. RESULTS: Among patients receiving NSAID that are CYP2C8/9 substrates the frequencies for carriers of variant alleles versus control patients were CYP2C8*3: 0.50 vs. 0.23 [odds ratio (OR); 95% confidence interval (CI)=3.4; 1.5-7.5; P=0.002], CYP2C9*2: 0.48 vs. 0.26 (OR; 95% CI=2.7; 1.2-5.8; P=0.013) and CYP2C9*3: 0.24 vs. 0.20 (OR; 95% CI=1.3; 0.5-3.1; P=0.578). The frequencies for carriers of the CYP2C8*3+CYP2C9*2 genotype were 0.40 vs. 0.15 (OR; 95% CI=3.7; 1.6-8.9; P=0.003). These findings were not influenced by sex, age, smoking or drinking habits. Among bleeding patients receiving NSAID that are not extensively metabolized by CYP2C8/9, no differences in genotypes or allele frequencies were observed as compared with control patients. CONCLUSION: The combined presence of CYP2C8*3 and CYP2C9*2 (CYP2C8*3+CYP2C9*2 genotype), is a relevant determinant in the risk to develop gastrointestinal bleeding in patients receiving NSAID that are CYP2C8/9 substrates.
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Blanco‐Fernández et al. (2008) conducted a cross-sectional in NSAID-related acute gastrointestinal bleeding (n=311). CYP2C8*3 and CYP2C9*2 genotypes vs. Non-carriers was evaluated on Acute gastrointestinal bleeding (OR 3.7, 95% CI 1.6-8.9, p=0.003). The CYP2C8*3+CYP2C9*2 genotype increased the risk of acute gastrointestinal bleeding in patients receiving CYP2C8/9 substrate NSAIDs (OR 3.7; 95% CI 1.6-8.9; P=0.003).
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