|(A;A)||2||>1.81x risk of GI bleeding with NSAID drugs|
|(A;G)||1.5||1.81x risk of GI bleeding with NSAID drugs|
|(G;G)||1||No increased risk of GI bleeding on NSAID drugs|
|qualified_impact||Insufficiently evaluated pharmacogenetic|
[PMID 19422321] In a 2009 article titled "Genetically based impairment in CYP2C8- and CYP2C9-dependent NSAID metabolism as a risk factor for gastrointestinal bleeding: is a combination of pharmacogenomics and metabolomics required to improve personalized medicine?" It is claimed that individuals carrying minor alleles of this SNP (usually heterozygotes, since minor homozygotes are rare) may show increased risk of developing acute gastrointestinal bleeding during the use of NSAIDs that are CYP2C8 or CYP2C9 substrates, such as aceclofenac, celecoxib, diclofenac, ibuprofen, indomethazine, lornoxicam, meloxicam, naproxen, piroxicam, tenoxicam and valdecoxib.
[PMID 18216720] In a 2008 article (reviewed in [PMID 19422321]) titled "Interaction of CYP2C8 and CYP2C9 genotypes modifies the risk for nonsteroidal anti-inflammatory drugs-related acute gastrointestinal bleeding," the study discovered that carriers of CYP2C8*3 (a minor allele of both rs10509681 and rs11572080) had a GI bleeding event risk OR=1.81 (95% CI=0.95–3.46; P=0.071) and risk increased if carriers drank more than 20g alcohol/day to an OR=1.99 (95% CI=1.06–3.74; P=0.034). As CYP2C8*3 and CYP2C9*2 rs1799853 variant alleles are in linkage disequilibrium, patients are likely to carry the risk allele to both 8*3 and 9*2, and when they do, The OR (95% CI) for carriers of such a genotype is increased to 1.94 (1.13–3.33), P=0.017.
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