Respiratory epithelial gene expression in patients with mild and severe cystic fibrosis lung disease

Jerry M. Wright, Christian A. Merlo, Jeffrey B. Reynolds, Pamela L. Zeitlin, Joe G.N. Garcia, William B. Guggino, Michael P. Boyle

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


Despite having identical cystic fibrosis transmembrane conductance regulator genotypes, individuals with ΔF508 homozygous cystic fibrosis (CF) demonstrate significant variability in severity of pulmonary disease. This investigation used high-density oligonucleotide microarray analysis of nasal respiratory epithelium to investigate the molecular basis of phenotypic differences in CF by (1) identifying differences in gene expression between ΔF508 homozygotes in the most severe 20th percentile of lung disease by forced expiratory volume in 1 s and those in the most mild 20th percentile of lung disease and (2) identifying differences in gene expression between ΔF508 homozygotes and age-matched non-CF control subjects. Microarray results from 23 participants (12 CF, 11 non-CF) met the strict quality control guidelines and were used for final data analysis. A total of 652 of the 11,867 genes identified as present in 75% of the samples were significantly differentially expressed in one of the three disease phenotypes: 30 in non-CF, 53 in mild CF, and 569 in severe CF. An analysis of genes differentially expressed by severity of CF lung disease demonstrated significant upregulation in severe CF of genes involved in protein ubiquination (P < 0.04), mitochondrial oxidoreductaseactivity (P < 0.01), and lipid metabolism (P < 0.03). Analysis of genes with decreased expression in patients with CF compared with control subjects demonstrated significant downregulation of genes involved in airway defense (P < 0.047) and protein metabolism (P < 0.048). This study suggests that differences in CF lung phenotype are associated with differences in expression of genes involving airway defense, protein ubiquination, and mitochondrial oxidoreductase activity and identifies specific new candidate modifiers of the CF phenotype.

Original languageEnglish (US)
Pages (from-to)327-336
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Issue number3
StatePublished - Sep 2006


  • Cystic fibrosis
  • Gene expression
  • Phenotype
  • Respiratory epithelium

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


Dive into the research topics of 'Respiratory epithelial gene expression in patients with mild and severe cystic fibrosis lung disease'. Together they form a unique fingerprint.

Cite this