HSP70-2 9.0 kb variant is in linkage disequilibrium with the HLA-B and DRB1* alleles associated with clozapine-induced agranulocytosis.
In order to extend the analysis of the association between class I and class II HLA markers and HSP-70 alleles, we studied the genetic polymorphism of HSP70-2 genes by restriction fragment length polymorphism analysis in a panel of HLA-homozygous cell lines carrying the HLA-B alleles known to be associated with clozapine-induced agranulocytosis. We have found a linkage disequilibrium between the 9.0 kb variant of HSP70-2 with the class I antigens HLA-B7, B38, and B44 and with the class II antigens HLA-DR2 and DR4. We discuss the importance of analyzing the variants of HSP70-2 in patients with agranulocytosis to confirm that the 9.0 kb allele is a genetic marker for the disease. If that is the case, HSP-70 variants could explain the different associations of HLA alleles in individuals of Jewish and non-Jewish ancestry because the HLA alleles are in linkage disequilibrium with the 9.0 kb band. We postulate that HSP-70 molecules could also play a significant role in determining the molecular mechanisms that induce agranulocytosis by clozapine.
Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, Mass 02115.
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D
Corzo
J J
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Yunis
E J
EJ
Yunis
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A
Howard
J A
JA
Lieberman
D000380:Agranulocytosis / Q000139:chemically induced* / Q000235:genetics; D003024:Clozapine / Q000009:adverse effects*; D014644:Genetic Variation; D015235:HLA-B Antigens / Q000235:genetics; D015802:HLA-DR2 Antigen / Q000235:genetics; D015804:HLA-DR4 Antigen / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D011110:Polymorphism, Genetic
D015235:HLA-B Antigens; D015802:HLA-DR2 Antigen; D015804:HLA-DR4 Antigen; D018840:HSP70 Heat-Shock Proteins; D003024:Clozapine