title: Drug-induced agranulocytosis: impact of different fcgamma receptor polymorphisms?
abstract: Drug-induced agranulocytosis is a rare but life-threatening side effect which is possibly based on immunogenetic mechanisms. Some studies regarding agranulocytosis induced by the atypical antipsychotic clozapine dealing with HLA subtyping and enzyme polymorphisms have been performed to elucidate its genetic background. To further screen possibly genetically based pathways of developing agranulocytosis, we assessed clinically relevant polymorphisms of immunoglobulin G or Fcgamma receptors in patients with clozapine-induced (n = 48), ticlopidine-induced (n = 11), thyroid inhibitors-induced agranulocytosis (n = 8), and controls (n = 75). We found significant age-related effects in each of the drug-induced agranulocytoses but no further associations that underline an effect of polymorphisms in FcgammaRIIa, FcgammaRIIIa, and FcgammaRIIIb genes on drug-induced agranulocytosis. Thus, Fcgamma receptors may not serve as a genetic marker to identify patients at risk for this life-threatening side effect.
authors.affiliation: Institute of Pharmacology, Ernst Moritz Arndt University, Greifswald, Germany.
authors.forename: Igor
authors.initials: I
authors.lastname: Mosyagin
authors.forename: Ingolf
authors.initials: I
authors.lastname: Cascorbi
authors.forename: Rainer
authors.initials: R
authors.lastname: Schaub
authors.forename: Timo
authors.initials: T
authors.lastname: Krüger
authors.forename: Michael
authors.initials: M
authors.lastname: Dettling
mesh_terms: D000328:Adult; D000380:Agranulocytosis / Q000097:blood / Q000139:chemically induced* / Q000235:genetics*; D014150:Antipsychotic Agents / Q000009:adverse effects; D013956:Antithyroid Agents / Q000009:adverse effects; D003024:Clozapine / Q000009:adverse effects; D004247:DNA / Q000235:genetics; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects; D005838:Genotype; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D017452:Receptors, IgG / Q000235:genetics* / Q000378:metabolism*; D013988:Ticlopidine / Q000009:adverse effects
chemical_list: D014150:Antipsychotic Agents; D013956:Antithyroid Agents; D005343:Fibrinolytic Agents; D017452:Receptors, IgG; D004247:DNA; D003024:Clozapine; D013988:Ticlopidine