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Letters to the Editor
January 2001

Genetic Determinants of Clozapine-Induced Agranulocytosis: Recent Results of HLA Subtyping in a Non-Jewish Caucasian Sample

Arch Gen Psychiatry. 2001;58(1):93-94. doi:10.1001/archpsyc.58.1.93

The incidence of agranulocytosis in clozapine-treated patients is comparatively high despite the undisputed clinical advantages of clozapine.1 The mechanisms of clozapine-induced agranulocytosis (CA) are debatable2; however, there are some findings indicative of an idiosyncratic drug reaction, pointing to a genetic basis of this adverse effect.3 Some studies suggest that specific HLA haplotypes are associated with a patient's susceptibility to developing CA.4-8 In these studies, HLA subtyping of Jewish and non-Jewish Caucasian patients with and without CA was performed. Clozapine-induced agranulocytosis was associated with HLA-B38, DRB1*0402, DRB4*0101, DQB1*0201, and DQB1*0302 haplotypes in Jewish and HLA-DR*02, DRB1*1601, DRB5*02, and DQB1*0502 in non-Jewish Caucasian patients4-7; the presence of HLA-B35 seemed to be a protective factor against CA in the latter group.8 However, each of these studies had statistical and/or methological shortcomings, such as small sample size, lack of clinical descriptions of study subjects, or insufficient information about the study design.

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