title: Impact of MIF gene promoter polymorphism on F508del cystic fibrosis patients.
abstract: Macrophage migration Inhibitory Factor (MIF) is a pro-inflammatory cytokine sustaining the acute response to gram-negative bacteria and a regulatory role for MIF in Cystic Fibrosis has been suggested by the presence of a functional, polymorphic, four-nucleotide repeat in this gene's promoter at position -794, with the 5-repeat allele displaying lower promoter activity. We aimed at assessing the association of this polymorphism with disease severity in a group of Cystic Fibrosis patients homozygous for F508del CFTR gene mutation. Genotype frequencies were determined in 189 Cystic Fibrosis and 134 control subjects; key clinical features of patients were recorded and compared among homozygous 5-allele patients and the other MIF genotypes. Patients homozygous for the 5-repeat allele of MIF promoter displayed a slower rate of lung function decline (p = 0.027) at multivariate survival analysis. Multiple regression analysis on age-normalized respiratory volume showed no association of the homozygous 5-repeat genotype with lung function under stable conditions and no correlation with P.aeruginosa chronic colonization. Therefore, only the Homozygous 5-repeat genotype at MIF -794 is associated with milder disease in F508del Cystic Fibrosis patients.
authors.affiliation: Cystic Fibrosis Centre, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Melotti
authors.affiliation: ARC-NET Research Centre and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mafficini
authors.affiliation: Pediatric Pulmonology & Cystic Fibrosis Unit, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lebecque
authors.affiliation: Cystic Fibrosis Centre, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Myriam
authors.initials: M
authors.lastname: Ortombina
authors.affiliation: Louvain Centre for Toxicology and Applied Pharmacology, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Teresinha
authors.initials: T
authors.lastname: Leal
authors.affiliation: Cystic Fibrosis Centre, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Emily
authors.initials: E
authors.lastname: Pintani
authors.affiliation: Centre for Human Genetics; Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Xavier
authors.initials: X
authors.lastname: Pepermans
authors.affiliation: ARC-NET Research Centre and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Sorio
authors.affiliation: Cystic Fibrosis Centre, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Baroukh Maurice
authors.initials: BM
authors.lastname: Assael
mesh_terms: D000328:Adult; D017668:Age of Onset; D000483:Alleles; D003550:Cystic Fibrosis / Q000453:epidemiology / Q000235:genetics* / Q000382:microbiology / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D005541:Forced Expiratory Volume; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008168:Lung / Q000382:microbiology / Q000503:physiopathology; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011550:Pseudomonas aeruginosa / Q000502:physiology; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D055815:Young Adult
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D019005:Cystic Fibrosis Transmembrane Conductance Regulator