HLA ASSOCIATIONS IN CLOZAPINE-INDUCED AGRANULOCYTOSIS

We previously reported preliminary results of association of clozapine -induced agranulocytosis (CA) with HLA-B38, DR4, DQ3 in five Ashkenazi Jewish patients and with HLA-DR2, DQ1 in four non-Jewish patients. In the present study, 31 additional patients with CA, 10 Ashkenazi Jewis h, and 21 of non-Jewish ancestry, were studied. HLA alleles and haplot ypes were compared among 52 patients (33 Ashkenazi Jewish, 19 non-Jewi sh) matched for ethnic background and clinical status. Our results sho w two associations and define the HLA allele markers for the Ashkenazi Jewish and non-Jewish haplotypes associated with CA. The most importa nt markers for susceptibility for CA in Ashkenazi Jewish patients were DRB10402, DQB1*0302, and DQA1*0301, and in non-Jewish patients, HLA- DR02, DQB1*0502, and DQA1*0102. HLA-DRB1*011 and DQB1*0301 were under represented in Ashkenazi Jewish patients when compared with controls. We hypothesize that genes of the major histocompatability complex, oth er than class I and class II, are responsible for CA; among them are t he variants of the heat-shock proteins 70 or the tumor necrosis factor loci. (C) 1995 by The American Society of Hematology.