HSP70-2 9.0 kb variant is in linkage disequilibrium with the HLA-B and DRB1* alleles associated with clozapine-induced agranulocytosis

J Clin Psychiatry. 1994 Sep:55 Suppl B:149-52.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Agranulocytosis / chemically induced*
  • Agranulocytosis / genetics
  • Clozapine / adverse effects*
  • Genetic Variation
  • HLA-B Antigens / genetics
  • HLA-DR2 Antigen / genetics
  • HLA-DR4 Antigen / genetics
  • HSP70 Heat-Shock Proteins / genetics*
  • Humans
  • Linkage Disequilibrium*
  • Polymorphism, Genetic

Substances

  • HLA-B Antigens
  • HLA-DR2 Antigen
  • HLA-DR4 Antigen
  • HSP70 Heat-Shock Proteins
  • Clozapine