title: Cystic fibrosis, disease severity, and a macrophage migration inhibitory factor polymorphism.
abstract: BACKGROUND
  Macrophage migration inhibitory factor (MIF) is a key proinflammatory mediator. It contributes toward an exaggerated gram-negative inflammatory response via its ability to induce Toll-like receptor-4 expression. Studies have shown that MIF knockout mice have less aggressive Pseudomonas infection (compared with wild-type).
  
  
  OBJECTIVE
  To assess whether a novel functional MIF polymorphism was associated with clinical prognosis in a patient cohort with chronic gram-negative infection, namely cystic fibrosis (CF).
  
  
  METHODS
  Collected genomic DNA was analyzed via polymerase chain reaction amplification for the polymorphic region for the CATT repeat polymorphism. Individuals may have a 5-, 6-, 7-, or 8-CATT tetranucleotide repeat unit on each allele. The 5-CATT repeat allele exhibits the lowest MIF promoter activity.
  
  
  RESULTS
  Patients with stable CF (n = 167) and a matched control group (n = 166) were enrolled. In patients with CF, the MIF5(+) group had a decreased incidence of Pseudomonas aeruginosa colonization (odds ratio, 0.25; 95% confidence interval, 0.09-0.65; p = 0.004) and a significant reduction in the risk of pancreatic insufficiency (odds ratio, 0.27; 95% confidence interval, 0.07-1.0; p = 0.05). A trend toward milder disease activity in the MIF5(+) group was seen with all other parameters.
  
  
  CONCLUSIONS
  The results support the concept of a regulatory role for MIF in CF.
authors.affiliation: F.R.C.P.I., Department of Medicine and Therapeutics, The Education Research Centre, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland. seamas.donnelly@ucd.ie
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Plant
authors.forename: Charles G
authors.initials: CG
authors.lastname: Gallagher
authors.forename: Richard
authors.initials: R
authors.lastname: Bucala
authors.forename: John A
authors.initials: JA
authors.lastname: Baugh
authors.forename: Sally
authors.initials: S
authors.lastname: Chappell
authors.forename: Linda
authors.initials: L
authors.lastname: Morgan
authors.forename: Clare M
authors.initials: CM
authors.lastname: O'Connor
authors.forename: Kevin
authors.initials: K
authors.lastname: Morgan
authors.forename: Seamas C
authors.initials: SC
authors.lastname: Donnelly
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D003550:Cystic Fibrosis / Q000235:genetics* / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index
chemical_list: C505032:CFTR protein, human; D008263:Macrophage Migration-Inhibitory Factors; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA