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Severe reaction to epilepsy drug linked to genetic variant
Researchers have discovered a genetic variant which significantly increases the risk of carriers being allergic to a common medication for epilepsy. The study, which included the UK’s Epilepsy Society, is published in the New England Journal of Medicine.
Carbamazepine is one of the most commonly prescribed drugs to counter epilepsy. It is also used to treat trigeminal neuralgia (a chronic pain disorder) and bipolar disorder. Although the medication is generally well tolerated, a minority of patients develop reactions. Around one in twenty will have a very mild reaction, but a small number will develop more serious – and potentially fatal – reactions, such as inflammation of the kidneys or a blistering skin rash.
A previous study found a strong correlation between the genetic variant HLA-B*1502 and severe allergic reaction to the drug amongst Asians of Han Chinese descent. However, as this variant is largely absent in people of European descent, it could not explain an allergic response to the drug in these populations.
An international collaboration, which includes researchers from Epilepsy Society investigating the genetics of epilepsy, conducted a genome-wide association study, examining 65 patients who suffered adverse reactions to the medication and compared their DNA to nearly 4,000 healthy controls. All patients were of European descent.
Despite the small patient cohort, the researchers were able to identify a genetic variant - HLA-A*3101 – which was a strong predictor of both mild and severe adverse reactions to carbamazepine. The variant has previously been correlated with a mild reaction to the drug amongst Asians of Han Chinese and Japanese descent. It falls within a region of the genome known to play an important role in the immune system and autoimmunity.
"We cannot say yet why this genetic variant increases the risk of a patient developing an adverse reaction to carbamazepine, but the association is very clear. It’s an important breakthrough," said Professor Sanjay Sisodiya from Epilepsy Society and one of the authors of the study. "Given the strength of the association, we should consider recommending testing for the variant before prescribing the drug."
Professor Sisodiya heads Epilepsy Society’s genetics research team which, working in collaboration with the EPIGEN consortium, is the world’s largest genetics research programme looking at epilepsy. An individual’s genetic make- up can affect their risk of developing epilepsy, the consequences and their response to treatments.
