Idiopathic pulmonary fibrosis: Update on genetic discoveries

Christine Kim Garcia

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease of the lungs that increases in prevalence with advanced age. Recent evidence indicates that mutations in genes of two different biologic pathways lead to the common phenotype of familial pulmonary fibrosis (FPF) and sporadic IPF. Mutations in the genes encoding the lung surfactant proteins C and A2 (SFTPC and SFTPA2, respectively) cause increased endoplasmic reticulum stress in type II alveolar epithelial cells. Mutations in the genes encoding telomerase (TERT and TERC) cause IPF through shortening of telomere lengths and probable exhaustion of lung stem cells. All of the mutations are individually rare, but, collectively, TERT mutations are the most common genetic defect found in FPF. The overall penetrance of pulmonary fibrosis in TERT mutation carriers is 40% in subjects with a mean age of 51 years. Penetrance increases with advanced age, is greater in males than in females, and is positively associated with fibrogenic environmental exposures. Short telomere lengths are found in patients with FPF and sporadic IPF without mutations in telomerase, suggesting that the biologic pathway of telomerase dysfunction provides a biologic explanation for the age-related prevalence of IPF. The molecular data of two seemingly unrelated biologic pathways - alveolar epithelial endoplasmic reticulum stress and telomerase dysfunction - are beginning to elucidate the pathogenesis of IPF. These results have potentially predictive and therapeutic value.

Original languageEnglish (US)
Pages (from-to)158-162
Number of pages5
JournalProceedings of the American Thoracic Society
Volume8
Issue number2
DOIs
StatePublished - May 1 2011

Fingerprint

Idiopathic Pulmonary Fibrosis
Pulmonary Fibrosis
Telomerase
Mutation
Endoplasmic Reticulum Stress
Penetrance
Pulmonary Surfactant-Associated Proteins
Genes
Telomere Shortening
Alveolar Epithelial Cells
Telomere
Environmental Exposure
Protein C
varespladib methyl
Lung Diseases
Stem Cells
Phenotype
Lung

Keywords

  • Genetics
  • Idiopathic pulmonary fibrosis
  • Surfactant proteins
  • Telomerase
  • Telomere length

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Idiopathic pulmonary fibrosis : Update on genetic discoveries. / Garcia, Christine Kim.

In: Proceedings of the American Thoracic Society, Vol. 8, No. 2, 01.05.2011, p. 158-162.

Research output: Contribution to journalArticle

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