Mitchell B. Balter Award. Human leukocyte antigen-A1 predicts a good therapeutic response to clozapine with a low risk of agranulocytosis in patients with schizophrenia

J Clin Psychopharmacol. 2001 Feb;21(1):4-7. doi: 10.1097/00004714-200102000-00002.


Several studies indicate an association between human leukocyte antigens (HLA) and clozapine-induced agranulocytosis. The authors have previously reported a significantly increased frequency of HLA-A1 among patients with schizophrenia who do not respond to conventional drugs, but do respond to clozapine treatment. In this study, the authors addressed the question of whether the same association is found in patients developing granulocytopenia or agranulocytosis. The frequency of the HLA-A1 allele in patients with clozapine-induced agranulocytosis or granulocytopenia was low (11.5%), whereas HLA-A1 was associated with a good therapeutic response to clozapine at an allele frequency of 58%. The frequency of HLA-A1 is 20% in the Finnish population. These results suggest that HLA-A1 may predict a good therapeutic outcome and a low risk of agranulocytosis and, thus, enable defining a subgroup of patients with schizophrenia in whom clozapine treatment could be started early to stop the disease from progressing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Agranulocytosis / chemically induced
  • Agranulocytosis / genetics*
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Clozapine / adverse effects
  • Clozapine / therapeutic use*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • HLA-A1 Antigen / genetics*
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Risk Factors
  • Schizophrenia / complications
  • Schizophrenia / drug therapy
  • Schizophrenia / genetics*


  • Antipsychotic Agents
  • HLA-A1 Antigen
  • Clozapine