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Single amino acid mutation of FCγ receptor is associated with the development of heparin‐induced thrombocytopenia
Author(s) -
Burgess Janette K.,
Lindeman Robert,
Chesterman Colin N.,
Chong Beng H.
Publication year - 1995
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1995.tb05383.x
Subject(s) - heparin , allele , monoclonal antibody , genotype , phenotype , platelet , antibody , immunology , biology , heparin induced thrombocytopenia , microbiology and biotechnology , mutation , population , subclass , platelet activation , receptor , arginine , genetics , amino acid , medicine , gene , biochemistry , environmental health
Summary. Heparin‐induced thrombocytopenia (HIT) is mediated by a heparin‐dependent antibody/platelet factor 4/heparin complex binding to platelets via the FCγ receptor (type IIA). A single base polymorphism at position 131 of FeγRIIA changes the native arginine to histidine. In the presence of murine monoclonal IgG 1 the former phenotype (FcγRIIA Arg131 ) is functionally characterized by strong platelet aggregation (high responder) and the latter (Fc7RIIA Hls131 ) by poor aggregation (low responder). In the presence of human IgGa the opposite response is observed. It has recently been shown that the heparin‐dependent antibody is predominantly of this subclass. We hypothesize that a relationship exists between FcγRIIA Hls131 and the development of HIT. We studied 24 normal individuals and 20 HIT patients using VM58, a murine monoclonal IgG 1 , to characterize the phenotype by platelet aggregrometry, and PCR products, amplified with primers bordering the FC7RIIA polymorphism and hybridized with oligonucleotide probes specific for the single base mutation, to determine the genotype. The distribution of phenotypes and genotypes in the two populations differed, with a greater prevalence of the FcγRIIA His131 allele in the HIT patient population. Homozygous Fc7RIIA Arg131 individuals were absent from this group. We conclude that the presence of the Fc7RIIA His131 allele is associated with a predisposition to HIT.