Human leukocyte antigens (HLA) and its association with skin rashes and drug induced hepatitis: The role of pharmacogenetics to predict anti-epileptic drug side-effect
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This study aims to investigate the individual responses of patients who developed a rash or drug-induced hepatitis due to an anti-epileptic drug (AED), and link this information to the genetic profile of each patient – in particular that for the human leukocyte antigens (HLA). The results will help to identify genetic markers that could predict when a patient is at risk of having side effects with a particular medication.
Previous experience has shown that individuals vary greatly in their responses to drugs. Although medication is effective and well tolerated in most patients side-effects can necessitate treatment changes. One of the most common, and potential serious, types of side effects to anti-epileptic drugs is hypersensitivity reactions - including generalised skin rashes, Steven Johnson Syndrome (SJS), and drug-induced hepatitis. It has been shown that genetic factors play an important role in determining an individual’s response to medication. Recently, the occurrence of SJS in Asian patients taking carbamazepine has been repeatedly associated with the carriage of a particular HLA antigen, HLA-B*1502. However, this association does not persist in non-Asian populations and HLA associations in other populations, or with other types of AED-induced hypersensitive reactions, have not yet been identified. Understanding why responses vary has the potential to improve the safety and effectiveness of medical treatment for various conditions.
This project will utilize an international unique cohort of more than 400 patients who have been prospectively enrolled and followed following starting treatment with an AED for the first time. The HLA profiles of patients who developed hypersensitivity reactions will be compared with those who took the same drug but did not develop any such reactions. The goal of this research is to eventually allow the choice of medication to be tailored to an individual’s specific genetic profile.
- Prof Terence O’Brien
- Dr Slave Petrovski
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