HLA associations in clozapine-induced agranulocytosis.
نویسندگان
چکیده
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 Jewish, and 21 of non-Jewish ancestry, were studied. HLA alleles and haplotypes were compared among 52 patients (33 Ashkenazi Jewish, 19 non-Jewish) matched for ethnic background and clinical status. Our results show two associations and define the HLA allele markers for the Ashkenazi Jewish and non-Jewish haplotypes associated with CA. The most important markers for susceptibility for CA in Ashkenazi Jewish patients were DRB1*0402, DQB1*0302, and DQA1*0301, and in non-Jewish patients, HLA-DR*02, DQB1*0502, and DQA1*0102. HLA-DRB1*011 and DQB1*0301 were underrepresented in Ashkenazi Jewish patients when compared with controls. We hypothesize that genes of the major histocompatability complex, other than class I and class II, are responsible for CA; among them are the variants of the heat-shock proteins 70 or the tumor necrosis factor loci.
منابع مشابه
Late Onset Agranulocytosis with Clozapine Associated with HLA DR4 Responding to Treatment with Granulocyte Colony-stimulating Factor: A Case Report and Review of Literature.
Agranulocytosis as a side effect of clozapine has been reported to be associated with initial phases of treatment, i.e., first six months. Agranulocytosis with clozapine during the initial phases of treatment has been linked to genetic vulnerability in the form of variations in the human leukocyte-antigen haplotypes. However, there is limited literature on late onset agranulocytosis with clozap...
متن کاملClozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles
Clozapine is a particularly effective antipsychotic medication but its use is curtailed by the risk of clozapine-induced agranulocytosis/granulocytopenia (CIAG), a severe adverse drug reaction occurring in up to 1% of treated individuals. Identifying genetic risk factors for CIAG could enable safer and more widespread use of clozapine. Here we perform the largest and most comprehensive genetic ...
متن کاملPharmacogenomic Study of Clozapine-Induced Agranulocytosis/Granulocytopenia in a Japanese Population
BACKGROUND Clozapine-induced agranulocytosis (CIA)/clozapine-induced granulocytopenia (CIG) (CIAG) is a life-threatening event for schizophrenic subjects treated with clozapine. METHODS To examine the genetic factor for CIAG, a genome-wide pharmacogenomic analysis was conducted using 50 subjects with CIAG and 2905 control subjects. RESULTS We identified a significant association in the huma...
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Introduction : clozapine is the first effective antipsychotic drug with the least extra pyramidal side effects and more agranulocytosis than other standard neuroleptics. Granolocytopenia or agranulocytosis occurs in 1 to 2 percent of all patients treated with clozapine. agranulocytosis due to clozapine is a fatal disorder that requires immediate clinical intervention. Method : this paper re...
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ورودعنوان ژورنال:
- Blood
دوره 86 3 شماره
صفحات -
تاریخ انتشار 1995