Pharmacogenetics of Gastrointestinal Bleeding

Gastrointestinal bleeding is a severe adverse effect occurring in subjects secondary to the use of nonsteroidal anti-inflammatory drugs (NSAIDs). The enzyme CYP2C9 is responsible for the elimination of most NSAIDs. Several polymorphisms have been observed in CYP2C9. Of these, the CYP2C9*3 allele, found in 12% of caucasian subjects, leads to reduced function of the enzyme.

We hypothesized that individuals carrying this mutation should be at higher risk of gastrointestinal bleeding since they display decreased elimination of some NSAIDs.

The purpose of this study is to determine whether the frequency for CYP2C9*3 variant allele is increased in subjects using NSAIDs metabolized by CYP2C9 in comparison with subjects under NSAIDs not metabolized by this enzyme.

The study groups consist of 200 patients suffering from gastrointestinal bleeding after NSAIDs use, divided in 100 patients using NSAIDs metabolized by CYP2C9 and 100 patients using other NSAIDs.

Inclusion criteria

• Upper gastrointestinal bleeding revealed by hematemesis, melena or lowering of at least 2g/dl of haemoglobin
• Endoscopic report of gastrointestinal ulcer or haemorrhagic lesion
• Immediate antecedents of NSAID therapy

Exclusion criteria

• Cirrhosis (Child B or C)
• Coma
• Concomitant therapy with substrates or inhibitors of CYP2C9 : ketoconazole, itraconazole, ritonavir, phenobarbital, rifampicin, depakine, phenytoin, St John's worts
• Patients treated by a NSAID metabolized by CYP2C9 and a NSAID not metabolized by CYP2C9