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 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.
Yunis
J J
JJ
Division of Immunogenetics, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Corzo
D
D
Salazar
M
M
Lieberman
J A
JA
Howard
A
A
Yunis
E J
EJ
D000328:Adult; D000380:Agranulocytosis / Q000139:chemically induced* / Q000235:genetics*; D000483:Alleles; D001483:Base Sequence; D003024:Clozapine / Q000009:adverse effects*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005787:Gene Frequency; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D015235:HLA-B Antigens / Q000235:genetics; D059945:HLA-B38 Antigen; D006683:HLA-DQ Antigens / Q000235:genetics; D015802:HLA-DR2 Antigen / Q000235:genetics; D015804:HLA-DR4 Antigen / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007585:Jews; D008297:Male; D008969:Molecular Sequence Data
D017931:DNA Primers; D015235:HLA-B Antigens; D059945:HLA-B38 Antigen; D006683:HLA-DQ Antigens; C051568:HLA-DQ1 antigen; C051569:HLA-DQ3 antigen; D015802:HLA-DR2 Antigen; D015804:HLA-DR4 Antigen; D003024:Clozapine