rs10509681

This is a CYP2C8 SNP. The CYP2C8*3 allele is mapped to both rs10509681 and rs11572080). 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. In a 2008 article (reviewed in ) 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. A 2013 NIH review titled "PharmGKB summary: very important pharmacogene information for cytochrome P450, family 2, subfamily C, polypeptide 8" reiterated that "some data suggest that the combined presence of minor risk alleles CYP2C8*3 (rs10509681 and rs11572080) and CYP2C9*2 rs1799853 is a determinant of NSAID-induced gastrointestinal bleeding." They cited .

C;C

The minor homozygous is rare but is likely to carry a higher risk.