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Published ahead of print on September 22, 2005, doi:10.1164/rccm.200412-1714OC

Am. J. Respir. Crit. Care Med., Volume 172, Number 11, December 2005, 1412-1415

A more recent version of this article appeared on December 1, 2005
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Submitted on December 21, 2004
Accepted on September 20, 2005

Cystic Fibrosis, Disease Severity and a Macrophage Migration Inhibitory Factor Polymorphism

Barry J Plant1, Charles G Gallagher1, Richard Bucala2, John A Baugh1, Sally Chappell3, Linda Morgan3, Clare M O'Connor1, Kevin Morgan3, and Seamas C Donnelly1*

1 Department of Medicine, University College Dublin, The Conway Institute of Biomolecular and Biomedical Research and The Dublin Molecular Medicine Centre, Dublin, Ireland, 2 Department of Medicine and Pathology, Yale University School of Medicine, New Haven, Connecticut, USA, 3 Queen's Medical Centre, University of Nottingham, Institute of Genetics, School of Molecular Medical Sciences, Nottingham, England, United Kingdom

* To whom correspondence should be addressed. E-mail: seamas.donnelly{at}ucd.ie.

RATIONALE: MIF is a key pro-inflammatory mediator. It contributes towards an exaggerated gramnegative inflammatory response via its ability to induce TLR4 (Toll like receptor-4) expression. Studies have shown that MIF knock-out mice have less aggressive pseudomonas infection (compared to 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. METHODS: Collected Genomic DNA was analysed via PCR 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: Stable CF patients (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 colonisation (Odds ratio 0.25; 95% confidence interval 0.09 to 0.65; p=0.004) and a significant reduction in the risk of pancreatic insufficiency (Odds ratio 0.27; 95% confidence interval 0.07 to 1.0; p =0.05). A trend towards 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: MIF, polymorphism, cystic fibrosis.




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