HLA-DQB1 6672 G>C is associated with the risk of clozapine-induced agranulocytosis in individuals of European ancestry

Introduction The atypical antipsychotic drug clozapine is the only effective drug for treatment-resistant schizophrenia, but also bears the risk of inducing severe adverse drug responses including neutropenia and agranulocytosis. Agranulocytosis and neutropenia occurs in about 1% and 3% of treated individuals. The aetiology is largely unknown, but there is evidence for contributing genetic factors. Identifying biomarkers could decrease blood monitoring effort and enable a more widespread use of clozapine. Several studies identified HLA variants (e.g. Athanasiou et al. 2011) and especially a polymorphism located in HLA-DBQ1 (6672 G>C, rs113332494) as associated with clozapine-induced agranulocytosis or neutropenia. Our study was conducted to replicate previous findings on HLA-DBQ1 6672 G>C.