Published ahead of print on September 22, 2005, doi:10.1164/rccm.200412-1714OC
© 2005 American Thoracic Society doi: 10.1164/rccm.200412-1714OC
Cystic Fibrosis, Disease Severity, and a Macrophage Migration Inhibitory Factor PolymorphismThe Conway Institute of Biomolecular and Biomedical Research and the Dublin Molecular Medicine Centre, Department of Medicine, University College Dublin, Dublin, Ireland; Institute of Genetics, School of Molecular Medical Sciences, Queen's Medical Centre,University of Nottingham, Nottingham, England; and Department of Medicine and Pathology, Yale University School of Medicine, New Haven, Connecticut Correspondence and requests for reprints should be addressed to Dr. Seamas C. Donnelly, M.D., F.R.C.P.I., Department of Medicine and Therapeutics, The Education Research Centre, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland. E-mail: seamas.donnelly{at}ucd.ie Rationale: 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). Objectives: 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. Measurements and Main 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.
Key Words: cystic fibrosis • macrophage migration inhibitory factor • polymorphism This article has been cited by other articles:
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