An update on the pharmacogenomics of NSAID metabolism and the risk of gastrointestinal bleeding.

: Several reports suggest a possible association between polymorphisms in the cytochrome P450 2C9 () gene and the risk for non-steroidal anti-inflammatory drug (NSAID)-related adverse gastrointestinal events, including gastrointestinal bleeding. Because findings were controversial, a systematic review and a meta-analysis of eligible studies on this putative association was conducted.: The authors have revised the relationship between polymorphisms and the risk of developing NSAID-related gastrointestinal bleeding, as well as other adverse gastrointestinal events, and performed meta-analyzes. The bias effect and potential sources of heterogeneity between studies was analyzed.: Individuals classified as poor metabolizers after genotyping (activity scores equal to 0 or 0.5) have an increased risk of developing NSAID-related gastrointestinal adverse events with an odds ratio (OR) = 1.86, ( = 0.004) and the OR for subjects with gastrointestinal bleeding is = 1.90, ( = 0.003). Gene-dose effect for variant alleles ( = 0.005 for all gastrointestinal adverse events, and = 0.0001 for bleeding patients) was observed. Also, there is an allele-specific effect in the association: is a poor risk predictor, whereas is a highly significant predictor of gastrointestinal adverse events ( = 0.006) and gastrointestinal bleeding ( = 0.0007).