Impact of MIF Gene Promoter Polymorphism on F508del Cystic Fibrosis Patients

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...

Full description

Saved in:
Bibliographic Details
Published in:PloS one Vol. 9; no. 12; p. e114274
Main Authors: Melotti, Paola, Mafficini, Andrea, Lebecque, Patrick, Ortombina, Myriam, Leal, Teresinha, Pintani, Emily, Pepermans, Xavier, Sorio, Claudio, Assael, Baroukh Maurice
Format: Journal Article
Language:English
Published: United States Public Library of Science 12.12.2014
Public Library of Science (PLoS)
Subjects:
Adult
Age
Age of Onset
Alleles
Biology and life sciences
Colonization
Comparative analysis
Cystic fibrosis
Cystic Fibrosis - epidemiology
Cystic Fibrosis - genetics
Cystic Fibrosis - microbiology
Cystic Fibrosis - physiopathology
Cystic fibrosis transmembrane conductance regulator
Cystic Fibrosis Transmembrane Conductance Regulator - genetics
Cytokines
Deoxyribonucleic acid
Diabetes
Disease
DNA
E coli
Female
Forced Expiratory Volume
Gene polymorphism
Genes
Genetic aspects
Genetic polymorphisms
Genomes
Genotype
Genotypes
Gram-negative bacteria
Homozygote
Humans
Infections
Inflammation
Leukocyte migration
Lung - microbiology
Lung - physiopathology
Lungs
Macrophage migration inhibitory factor
Macrophage Migration-Inhibitory Factors - genetics
Macrophages
Male
Medicine and Health Sciences
Multiple regression analysis
Mutation
Patients
Physical Sciences
Point mutation
Polymorphism
Polymorphism, Genetic
Promoter Regions, Genetic - genetics
Pseudomonas aeruginosa
Pseudomonas aeruginosa - physiology
Regression analysis
Repetitive Sequences, Nucleic Acid - genetics
Research and Analysis Methods
Respiratory function
Rheumatoid arthritis
Sepsis
Young Adult
Belgium
Italy
ISSN:1932-6203, 1932-6203
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: PM AM CS BMA TL. Performed the experiments: MO XP. Analyzed the data: PM AM PL EP XP TL. Contributed reagents/materials/analysis tools: MO XP. Wrote the paper: AM PM PL MO TL EP XP CS BMA.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0114274