Principal Investigator: Professor Sir Munir Pirmohamed
Institution: University of LiverpoolTags: 20887, Gastrointestinal, NSAID, Pharmacogenomics, Toxicity, Ulcer
1a: The primary aim is to identify risk factors (genetic and non-genetic) which may predispose individuals taking non-steroidal anti-inflammatory drugs (NSAIDs) to upper gastrointestinal (GI) ulceration. This project will form part of an existing programme of research which aims to better understand the mechanisms of NSAID ulceration and ultimately develop better therapeutic strategies for both prevention and treatment of this adverse drug reaction.
1b: NSAIDs are widely prescribed and purchased “over the counter” in the UK. Approximately 1-5% of those taking NSAIDs will develop symptomatic upper gastrointestinal injury within one year of commencing treatment. This represents a large number of individuals and a significant healthcare burden. This project therefore falls in to the UK Biobanks’ general aim of “improving the prevention, diagnosis and treatment of a wide range of serious and life-threatening illnesses”.
1c: This project will use quantitative analysis to explore genetic variants and biological measurements collected by UK Biobank and their association with upper gastrointestinal ulceration caused by non-steroidal anti-inflammatory drugs. We will attempt to replicate findings in other Biobanks and patient cohorts.
1d: Initial searches of the full cohort suggest that there are 3639 patients with a recorded gastric ulceration. Additionally there are >70,000 records of patients taking aspirin and >80,000 records of non-aspirin NSAIDs. It is anticipated that, after careful analysis of the data, the cross-section of patients both with a record of NSAID and with history of GI ulceration would form the cases with those on NSAIDs but with no ulceration and those with ulcers not on NSAIDs as two sets of controls.