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Genetics of clozapine-associated neutropenia: recent advances, challenges and future perspective

Legge, Sophie E. and Walters, James T.R. 2019. Genetics of clozapine-associated neutropenia: recent advances, challenges and future perspective. Pharmacogenomics 20 (4) , pp. 279-290. 10.2217/pgs-2018-0188

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Clozapine is the only effective antipsychotic for treatment-resistant schizophrenia but remains widely under prescribed, at least in part due to its potential to cause agranulocytosis and neutropenia. In this article, we provide an overview of the current understanding of the genetics of clozapine-associated agranulocytosis and neutropenia. We now know that the genetic etiology of clozapine-associated neutropenia is complex and is likely to involve variants from several genes including HLA-DQB1, HLA-B and SLCO1B3/SLCO1B7. We describe recent findings relating to the Duffy-null genotype and its association with benign neutropenia in individuals with African ancestry. Further advances will come from sequencing studies, large, cross-population studies and in understanding the molecular mechanisms underlying these associations.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Future Medicine
ISSN: 1462-2416
Date of First Compliant Deposit: 8 January 2019
Date of Acceptance: 7 January 2019
Last Modified: 28 Jun 2019 16:07

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