Pharmacogenetics of Gastrointestinal Bleeding

Study Overview
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Brief Summary
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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 several NSAIDs. This protein is inactive in 12% of the subjects because of genetic mutations. We hypothesized that individuals carrying such mutations should be at higher risk of gastrointestinal bleeding since they display decreased NSAIDs elimination.

Detailed Description
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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.

Official Title
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Pharmacogenetics of Gastrointestinal Bleeding Under Nonsteroidal Anti-inflammatory Drugs : the Role of Cytochrome P450 2C9

Conditions
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Gastrointestinal Hemorrhage, Stomach Ulcer, Non-steroidal Anti-inflammatory Drug Sensitivity

Intervention / Treatment
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* Procedure: CY2PC9 genotyping


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: CY2PC9 genotyping|CY2PC9 genotyping|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gastrointestinal haemorrhage, stomach ulcer, anti-inflammatory agents, non-steroidal, CYP2C9 protein, human, genotype, pharmacogenetics