Clozapine is the most effective antipsychotic medication, but its use is limited because it can cause serious blood-related side effects, including a dangerous drop in white blood cells (agranulocytosis). Currently, there is no way to predict or prevent this risk, though it is likely linked to how clozapine is processed in the body.
Researchers have studied genetic factors that influence clozapine metabolism and its side effects, but only a few genetic markers have been identified. In this study, the largest available genetic dataset on clozapine metabolism and agranulocytosis was analysed using advanced statistical methods to identify new genetic links. The researchers found two previously unknown genetic markers related to how clozapine is metabolised, which were confirmed in a group of 392 patients taking clozapine. They also identified five genetic markers associated with the risk of agranulocytosis after adjusting for variations in white blood cell levels.
Further analysis suggested that people who metabolise clozapine more slowly may be at a higher risk of reduced white blood cell counts. Additionally, individuals genetically predisposed to low neutrophil levels may have a slightly increased risk of developing agranulocytosis from clozapine.
These findings highlight shared genetic factors influencing both clozapine metabolism and blood cell counts. This knowledge could help develop models to predict who might be at risk for agranulocytosis, potentially improving the safety of clozapine treatment.
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