Abstract
Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia (IIP), is characterized by irreversible scarring of the lung parenchyma and progressive decline in lung function leading to eventual respiratory failure. The prognosis of IPF is poor with a median survival of 3–5 years after diagnosis and no curative medical therapies. Although the pathogenesis of IPF is not well understood, there is a growing body of evidence that genetic factors contribute to disease risk. Recent studies have identified common and rare genetic variants associated with both sporadic and familial forms of pulmonary fibrosis, with at least one-third of the risk for developing fibrotic IIP explained by common genetic variants. The IPF-associated genetic loci discovered to date are implicated in diverse biological processes, including alveolar stability, host defense, cell–cell barrier function, and cell senescence. In addition, some common variants have also been associated with distinct clinical phenotypes. Better understanding of how genetic variation plays a role in disease risk and phenotype could identify potential therapeutic targets and inform clinical decision-making. In addition, clinical studies should be designed controlling for the genetic backgrounds of subjects, since clinical outcomes and therapeutic responses may differ by genotype. Further understanding of these differences will allow the development of personalized approaches to the IPF management.
Highlights
Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias (IIPs)
Familial studies have identified FIPassociated variants related to alveolar stability [SFTPC [12, 13], SFTPA1 [14], SFTPA2 [15], ATP-binding cassette-type 3 (ABCA3) [16], and NAF1 [17]] as well as five genes linked to telomere biology [TERT [18], TERC [18], DKC1 [19], TINF2 [7, 20], RTEL1 [21,22,23], and PARN] [24]
More recent studies have found an association between numerous genes in the telomerase maintenance pathway and familial interstitial pneumonia (FIP), including those related to catalytic activity (TERT and TERC) [7, 32] and telomere stabilization (DKC1, PARN, and RTELI) [19, 21]
Summary
Recent studies have identified common and rare genetic variants associated with both sporadic and familial forms of pulmonary fibrosis, with at least one-third of the risk for developing fibrotic IIP explained by common genetic variants. Better understanding of how genetic variation plays a role in disease risk and phenotype could identify potential therapeutic targets and inform clinical decision-making. Clinical studies should be designed controlling for the genetic backgrounds of subjects, since clinical outcomes and therapeutic responses may differ by genotype. Further understanding of these differences will allow the development of personalized approaches to the IPF management
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