title: Association of IRF5 polymorphisms with susceptibility to hemophagocytic lymphohistiocytosis in children.
abstract: BACKGROUND
  Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome and has a varied genetic background. The polymorphism of interferon regulatory factor 5 gene (IRF5) was reported to be associated with susceptibility to macrophage activation syndrome. IRF5 acts as a master transcription factor in the activation of pro-inflammatory cytokines. We assessed associations of IRF5 gene polymorphisms with susceptibility to secondary HLH.
  
  
  METHODS
  Three IRF5 single nucleotide polymorphisms (rs729302, rs2004640, and rs2280714) were genotyped using TaqMan assays in 82 secondary HLH patients and 188 control subjects.
  
  
  RESULTS
  There was a significant association of the GT/TT genotype at rs2004640 with secondary HLH susceptibility (p < 0.01). The IRF5 haplotype (rs729302 A, rs2004640 T, and rs2280714 T) was associated with secondary HLH susceptibility (p < 0.01).
  
  
  CONCLUSIONS
  These findings indicate that IRF5 is a genetic factor influencing the susceptibility to secondary HLH and that the IRF5-associated immune response contributes to the pathogenesis of HLH.
authors: Department of Pediatrics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors: Masakatsu
authors: M
authors: Yanagimachi
authors: Hiroaki
authors: H
authors: Goto
authors: Takako
authors: T
authors: Miyamae
authors: Keisuke
authors: K
authors: Kadota
authors: Tomoyuki
authors: T
authors: Imagawa
authors: Masaaki
authors: M
authors: Mori
authors: Hidenori
authors: H
authors: Sato
authors: Ryu
authors: R
authors: Yanagisawa
authors: Tetsuji
authors: T
authors: Kaneko
authors: Satoshi
authors: S
authors: Morita
authors: Eiichi
authors: E
authors: Ishii
authors: Shumpei
authors: S
authors: Yokota
mesh_terms: D000293:Adolescent; D001171:Arthritis, Juvenile / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000235:genetics*; D051359:Lymphohistiocytosis, Hemophagocytic; D008262:Macrophage Activation / Q000235:genetics; D008297:Male; D011110:Polymorphism, Genetic; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D016207:Cytokines; C431713:IRF5 protein, human; D018836:Inflammation Mediators; D050835:Interferon Regulatory Factors