HS70-2 9.0-KB VARIANT IS IN LINKAGE DISEQUILIBRIUM WITH THE HLA-B ANDDRB1-ASTERISK 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 polym orphism of HSP70-2 genes by restriction fragment length polymorphism a nalysis in a panel of HLA-homozygous cell lines carrying the HLA-B all eles known to be associated with clozapine-induced agranulocytosis. We have found a linkage disequilibrium between the 9.0 kb variant of HSP 70-2 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 t he variants of HSP70-2 in patients with agranulocytosis to confirm tha t the 9.0 kb allele is a genetic marker for the disease. If that is th e case, HSP-70 variants could explain the different associations of HL A alleles in individuals of Jewish and non-Jewish ancestry because the HLA alleles are in linkage disequilibrium with the 9.0 kb band. We po stulate that HSP-70 molecules could also play a significant role in de termining the molecular mechanisms that induce agranulocytosis by cloz apine.