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Clozapine-induced agranulocytosis in schizophrenic Caucasians: confirming clues for associations with human leukocyte class I and II antigens

The Pharmacogenomics Journal volume 7, pages 325–332 (2007)Cite this article

Abstract

Clozapine-induced agranulocytosis (CA) is still among the least understood adverse drug reactions in psychopharmacology. In particular, its genetic background is far from being clarified. Within the framework of a case–control study, we performed human leukocyte antigen (HLA) genotyping and haplotype analyses in 42 non-Jewish Caucasian schizophrenic patients (N=42) suffering from CA and 75 non-Jewish Caucasian schizophrenic patients treated with clozapine without developing CA. While controlling for age (P<0.0001) and sex (P=0.835), testing of the alleles from both HLA-loci resulted in borderline results for Cw2 (P=0.085, odds ratio (OR)=0.36, 95% confidence interval (CI): 0.08–1.23), Cw7 (P=0.058, OR=2.0, 95% CI: 0.87–4.63) and DRB5*0201 (P=0.005, adjusted OR=22.15). For haplotype analysis, we obtained significant association results with CA for the two-locus haplotypes HLA-Cw-B (P=0.022) and HLA-DRB5-DRB4 (P=0.050), and for the three-locus haplotype HLA-Cw-B-DRB5 (P=0.030). The complex nature of CA implies that many genes might play a role, but currently, only HLA associations with CA are identified as clinically relevant.

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Acknowledgements

This study was supported by Grant 01 EC 9406 from the German Federal Ministry of Education and Research. We thank all participating patients and supporting doctors.

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Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Charité-University Medicine Berlin, Berlin, Germany

    M Dettling & C Opgen-Rhein

  2. Department of Pharmacology, Institute of Pharmacology, University Hospital Schleswig-Holstein, Kiel, Germany

    I Cascorbi

  3. Department of Gerontopsychiatry, Center for Psychiatry, Weinsberg, Germany

    R Schaub

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  1. M Dettling
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  2. I Cascorbi
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  3. C Opgen-Rhein
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  4. R Schaub
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Correspondence to M Dettling.

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Dettling, M., Cascorbi, I., Opgen-Rhein, C. et al. Clozapine-induced agranulocytosis in schizophrenic Caucasians: confirming clues for associations with human leukocyte class I and II antigens. Pharmacogenomics J 7, 325–332 (2007). https://doi.org/10.1038/sj.tpj.6500423

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