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IgG- Fcγ- receptor polymorphisms in drug-induced-induced agranulocytosis
The pathomechanisms of clozapine-induced agranulocytosis are considered controversial, immune and/or toxic mechanisms are favoured (1)To further examine the immunogenetic hypothesis of clozapine-induced agranulocytosis we performed genotyping of IgG Fcγ receptor polymorphisms in patients suffering from agranulocytosis induced by clozapine (N=49), ticlopidine (N=11) thyreostatics (N=8) other drugs (N=12) and controls (n=75). Fcγ receptors are protective for antigens by forming an antigen antibody complex, and are located on the surface of macrophages, neutrophils and natural killer cells. The responsible gene is located on chromosome 1q23-q24. Genotyping included examination of polymorphisms of RIIA (associated to heparine –induced thrombocytopenia), RIIB (activation of NADPH-oxidase) and RIIIB-receptors (located on neutrophil granulocytes). We did not find statistically different distribution of polymorphisms between patients and controls.
1. Dettling M, Schaub RT, Müller-Oerlinghausen B, Roots I, Cascorbi I: Further evidence of human leukocyte antigen-encoded susceptibility to clozapine-induced agranulocytosis independent of ancestry. Pharmacogenetics 2001. 11: 135–141.
2. Bux-J: Molecular nature of antigens implicated in immune neutropenias. Int J Hematol 2002. 76: 399–403.