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REPLICATION OF TWO INDEPENDENT LOCI IN HLA-DQB1 AND HLA-B CONTRIBUTING TO THE RISK OF CLOZAPINE-INDUCED AGRANULOCYTOSIS
- Source :
- European Neuropsychopharmacology. 29:S939
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Background 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 like 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 contributing to the risk of agranulocytosis. The Clozapine-Induced Agranulocytosis Consortium (CIAC) identified two independent loci in the major histocompatibility complex genome-wide associated with clozapine-induced agranulocytosis: A single amino acid in HLA-DQB1 (126Q) (OR=0.19, P=4.7E−14) and an amino acid change in HLA-B (158 T) (OR=3.3, P=6.4E−10). Our study was performed to replicate these interesting findings. Methods 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 like 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 contributing to the risk of agranulocytosis. The Clozapine-Induced Agranulocytosis Consortium (CIAC) identified two independent loci in the major histocompatibility complex genome-wide associated with clozapine-induced agranulocytosis: A single amino acid in HLA-DQB1 (126Q) (OR=0.19, P=4.7E−14) and an amino acid change in HLA-B (158 T) (OR=3.3, P=6.4E−10). Our study was performed to replicate these interesting findings. Results HLA-DQB1 (126Q) was associated with agranulocytosis (OR=0.12, P=5.25E-05) and neutropenia (OR=0.18, P=7.34E-06), whereas HLA-B (158 T) was associated with neutropenia only (OR=2.45, P=1.32E-02). The HLA-DQB1 signal was mainly driven by agranulocytosis cases. Discussion We were able to replicate previous findings. Our study gives further evidence for the implication of immunological pathways and especially HLA-DQB1 in agranulocytosis and neutropenia.
- Subjects :
- Pharmacology
Drug
HLA-DQB1
medicine.drug_class
business.industry
media_common.quotation_subject
Atypical antipsychotic
Human leukocyte antigen
Neutropenia
medicine.disease
HLA-B
Psychiatry and Mental health
Neurology
Schizophrenia
Immunology
medicine
Pharmacology (medical)
Neurology (clinical)
business
Biological Psychiatry
Clozapine
media_common
medicine.drug
Subjects
Details
- ISSN :
- 0924977X
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- European Neuropsychopharmacology
- Accession number :
- edsair.doi...........564901e9ac89b1b025fbe66f53b849f1