title: High frequency of QPY allele and linkage disequilibrium of granzyme-B in Epstein-Barr-virus-associated hemophagocytic lymphohistiocytosis.
abstract: Mediation of Epstein-Barr virus (EBV)-specific cytotoxicity in T lymphocyte via the perforin/granzyme pathway has been demonstrated; therefore, a study involving cytolytic molecules was essential for the clarification of hemophagocytic lymphohistiocytosis (HLH) pathogenesis. This investigation, which analysed the frequency of three allelic mutations of granzyme-B (55Q/R, 95P/A and 247Y/H) in patients with EBV-HLH and infectious mononucleosis, identified the high prevalence of the QPY haplotype in EBV-HLH patients in comparison with healthy controls. A > G polymorphism was also detected in intron 5; furthermore, nearly complete linkage disequilibrium was observed among these polymorphisms. The recessive role of the QPY haplotype of granzyme-B might be responsible for the pathogenesis of EBV-HLH. Cytotoxicity and DNA fragmentation of cytotoxic T lymphocytes did not differ among patients characterized by the QPY/QPY, RAH/RAH and QPY/RAH genotypes. This finding suggested that DNA fragmentation in target cells is mediated not only by granzyme-B but also by other molecules, including other granzymes or Fas.
authors.affiliation: Department of Pediatrics, Saga University, Saga, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Zaitsu
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: E
authors.initials: E
authors.lastname: Ishii
authors.forename: T
authors.initials: T
authors.lastname: Teramura
authors.forename: N
authors.initials: N
authors.lastname: Nakadate
authors.forename: M
authors.initials: M
authors.lastname: Sako
authors.forename: N
authors.initials: N
authors.lastname: Sakata
authors.forename: H
authors.initials: H
authors.lastname: Wakiguchi
authors.forename: M
authors.initials: M
authors.lastname: Hirose
authors.forename: M
authors.initials: M
authors.lastname: Imayoshi
authors.forename: Y
authors.initials: Y
authors.lastname: Ogata
authors.forename: S
authors.initials: S
authors.lastname: Imashuku
authors.forename: Y
authors.initials: Y
authors.lastname: Hamasaki
authors.forename: M
authors.initials: M
authors.lastname: Yasukawa
mesh_terms: D020022:Genetic Predisposition to Disease; D053804:Granzymes; D004854:Herpesvirus 4, Human / Q000378:metabolism; D015616:Histiocytosis, Non-Langerhans-Cell / Q000235:genetics* / Q000276:immunology / Q000821:virology; D015810:Linkage Disequilibrium; D017354:Point Mutation; D012697:Serine Endopeptidases / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases