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Over 30 million people worldwide use aspirin and other non-aspirin non-steroidal antiinflammatory drugs (NSAID) on a daily basis. It is estimated that over 25% of patients treated for arthritis with NSAIDs have experienced gastrointestinal (GI) complications that required hospital admission and 60% of deaths from adverse drug reactions (ADRs) are attributable to NSAID use. Significant non-genetic risk factors for the development of NSAID-related gastrointestinal complications include gender, H. pylori infection, and concomitant medications. Three genes (UGT1A6, PAI-1 and EYA1) with biological plausibility for roles in NSAID-related ulcers were analysed. Our analysis of genetic risk factors for NSAID-related GI complications in 1197 case-control subjects showed no association between a UGT1A6 polymorphism and NSAIDinduced GI toxicity (p=0.052). Furthermore, a meta-analysis of UGT1A6 studies confirmed that there was no association between NSAID-related GI complications and UGT1A6. The PAI-1 4G/5G polymorphism was also not associated with NSAID-related ulcers and bleeding (n=756), while the EYA1 rs12678747 single nucleotide polymorphism (SNP) was significantly (p |
