title: A functional promoter haplotype of macrophage migration inhibitory factor is linked and associated with juvenile idiopathic arthritis.
abstract: OBJECTIVE
  To establish linkage and replicate the association of macrophage migration inhibitory factor (MIF) with juvenile idiopathic arthritis (JIA).
  
  
  METHODS
  Three hundred twenty-one Caucasian simplex families from the UK were genotyped for polymorphisms of MIF using SNaPshot ddNTP primer extension, or by a fluorescently labeled primer method, and capillary gel electrophoresis. The functional significance of the promoter polymorphisms was studied using luciferase-based reporter gene assays in human T lymphoblast and epithelial cell lines.
  
  
  RESULTS
  MIF was linked and associated with JIA (P = 0.0016). Specifically, a 2-point promoter haplotype, CATT(7)-MIF-173*C, was found to be transmitted in excess (38 transmitted: 21 not transmitted) in the JIA patients. Conditional extended transmission disequilibrium test and pairwise extended transmission disequilibrium test predicted functional interaction between the 2 polymorphic positions. The interaction of the CATT repeat with MIF-173*G/C was found to be specific to the cell type.
  
  
  CONCLUSIONS
  Replication of an association and linkage of MIF with JIA has been established. Functional interaction between the polymorphic positions on the linked haplotype has also been shown. The molecular mechanism of this interaction is currently being investigated.
authors.affiliation: Arthritis Research Campaign/Epidemiology Unit, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK. Rachelle@fs1.ser.man.ac.uk
authors.forename: Rachelle
authors.initials: R
authors.lastname: Donn
authors.forename: Zaynab
authors.initials: Z
authors.lastname: Alourfi
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Zeggini
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lamb
authors.forename: Francine
authors.initials: F
authors.lastname: Jury
authors.forename: Mark
authors.initials: M
authors.lastname: Lunt
authors.forename: Christina
authors.initials: C
authors.lastname: Meazza
authors.forename: Fabrizio
authors.initials: F
authors.lastname: De Benedetti
authors.forename: Wendy
authors.initials: W
authors.lastname: Thomson
authors.forename: David
authors.initials: D
authors.lastname: Ray
mesh_terms: D001171:Arthritis, Juvenile / Q000097:blood / Q000235:genetics*; D002097:C-Reactive Protein / Q000378:metabolism; D002460:Cell Line; D017930:Genes, Reporter; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D020545:Respiratory Mucosa / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology; D014162:Transfection
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D002097:C-Reactive Protein