title: Genetic loci contributing to hemophagocytic lymphohistiocytosis do not confer susceptibility to systemic-onset juvenile idiopathic arthritis.
abstract: OBJECTIVE
  To investigate whether single-nucleotide polymorphisms (SNPs) within the genes PRF1, GZMB, UNC13D, and Rab27a, which are involved in natural killer cell dysfunction and known to contribute to the risk of hemophagocytic lymphohistiocytosis (HLH), confer an increased risk of susceptibility to systemic-onset juvenile idiopathic arthritis (JIA).
  
  
  METHODS
  Four SNPs across the PRF1 gene locus, 5 for GZMB, 7 for UNC13D, and 11 for Rab27a were investigated using MassArray genotyping in 133 UK Caucasian patients with systemic-onset JIA and 384 ethnically matched unrelated control subjects. Additional control genotypes were accessed from the data generated by the Wellcome Trust Case Control Consortium.
  
  
  RESULTS
  No significant association was found between any SNP within the 4 selected loci and systemic-onset JIA, by either single-point or haplotype analysis.
  
  
  CONCLUSIONS
  The results of this study demonstrate that genes involved in HLH do not confer a significant risk of association with systemic-onset JIA.
authors.affiliation: Arthritis Research Campaign Epidemiology Unit, University of Manchester, Manchester, UK. Rachelle.donn@manchester.ac.uk
authors.forename: Rachelle
authors.initials: R
authors.lastname: Donn
authors.forename: Stuart
authors.initials: S
authors.lastname: Ellison
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lamb
authors.forename: Thomas
authors.initials: T
authors.lastname: Day
authors.forename: Eileen
authors.initials: E
authors.lastname: Baildam
authors.forename: Athimalaipet V
authors.initials: AV
authors.lastname: Ramanan
mesh_terms: D001171:Arthritis, Juvenile / Q000235:genetics*; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D053804:Granzymes / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D051359:Lymphohistiocytosis, Hemophagocytic / Q000235:genetics*; D008262:Macrophage Activation; D008565:Membrane Proteins / Q000235:genetics*; D054353:Perforin; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics*; D012307:Risk Factors; D020691:rab GTP-Binding Proteins / Q000235:genetics*; D000075745:rab27 GTP-Binding Proteins
chemical_list: D008565:Membrane Proteins; C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; C507969:UNC13D protein, human; D000075745:rab27 GTP-Binding Proteins; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; C066694:RAB27A protein, human; D020691:rab GTP-Binding Proteins