Clinical data of 187 Cystic Fibrosis patients homozygous for the F508del mutation according to the genotype for the <i>MIF</i> gene -CATT repeat at position −794.

<p>Data are presented as mean and 95% Confidence Interval (95% CI). FEV1: forced expiratory volume in one second; BMI: body mass index; cc by PA: chronic colonization by <i>P. aeruginosa</i>.</p><p>* CF specific percentile according to Kulich <i>et al</i>, <i>Am J Respir Crit Care Med</i>, 2005.</p><p>Clinical data of 187 Cystic Fibrosis patients homozygous for the F508del mutation according to the genotype for the <i>MIF</i> gene -CATT repeat at position −794.</p

Cox regression analysis for age at first acute episode with FEV1 <60% of predicted value on 185 Cystic Fibrosis patients homozygous for the F508del mutation.

<p>Number of patients with acute episode  = 119</p><p>Number of censored patients = 66</p><p>Overall significance p-value  = 0.0010</p><p>MIF-CATT genotype: <i>MIF</i> gene -CATT repeat genotype at position −794</p><p>95% CI  = 95% Confidence Interval</p><p>Cox regression analysis for age at first acute episode with FEV1 <60% of predicted value on 185 Cystic Fibrosis patients homozygous for the F508del mutation.</p

Multiple regression analysis of FEV1 (Kulich)^* data on 189 Cystic Fibrosis patients homozygous for the F508del mutation.

<p>Overall R² = 0.274; multiple correlation coefficient  = 0.524</p><p>Overall significance p-value<0.0001;</p><p>FEV1: forced expiratory volume in one second; cc by PA: chronic colonization by <i>P. aeruginosa</i>. MIF-CATT genotype: <i>MIF</i> gene -CATT repeat genotype at position -794</p><p>*CF specific percentile according to Kulich <i>et al</i>, <i>Am J Respir Crit Care Med</i>, 2005.</p><p>Multiple regression analysis of FEV1 (Kulich)^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0114274#nt113" target="_blank">*</a>} data on 189 Cystic Fibrosis patients homozygous for the F508del mutation.</p

Characteristics of 189 Cystic Fibrosis patients homozygous for the F508del mutation recruited from 2 different European centers.

<p>Continuous data are presented as mean ± SD unless otherwise stated; categorical data are presented as counts and proportions. FEV1: forced expiratory volume in one second; cc by PA: chronic colonization by <i>P. aeruginosa.</i> The most recent FEV1 was used for each patient. MIF-CATT: <i>MIF</i> gene -CATT repeat genotype at position -794</p><p>* CF specific percentile according to Kulich <i>et al</i>, <i>Am J Respir Crit Care Med</i>, 2005.</p><p>Characteristics of 189 Cystic Fibrosis patients homozygous for the F508del mutation recruited from 2 different European centers.</p

Lung function decline in 185 Cystic Fibrosis patients grouped according to <i>MIF</i> -794 CATT genotypes.

<p>Kaplan-Meier plots relative to age at first acute episode with FEV1 <60% of predicted value. (A) Comparison between patients with MIF 5-5 (homozygous 5-CATT repeats) vs. not 5-5 genotype; (B) comparison between patients with at least one 5-CATT allele vs. the others. Ticks indicate censored subjects follow-up times. “Number at risk” at the bottom indicates the number of patients without acute episodes at a given time interval and whose follow- up extends at least that far into the curve.</p

Impact of <i>MIF</i> Gene Promoter Polymorphism on F508del Cystic Fibrosis Patients

<div><p>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 <i>CFTR</i> 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 <i>MIF</i> genotypes. Patients homozygous for the 5-repeat allele of <i>MIF</i> 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 <i>P.aeruginosa</i> chronic colonization. Therefore, only the Homozygous 5-repeat genotype at <i>MIF</i> −794 is associated with milder disease in F508del Cystic Fibrosis patients.</p></div