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Genetics of Pulmonary Fibrosis

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Idiopathic Pulmonary Fibrosis

Part of the book series: Respiratory Medicine ((RM))

Abstract

Genetic sequence variants have been linked to familial pulmonary fibrosis (FPF). Many of the same genetic mechanisms implicated in FPF are relevant to sporadic interstitial lung disease (ILD) and, especially, idiopathic pulmonary fibrosis (IPF). Thus, these genetic insights have begun to reveal the molecular basis of a disease that was previously thought to be unknown. A common variant within the promoter of the MUC5B gene is the most replicated single nucleotide polymorphism linked to familial and sporadic forms of IPF as well as early radiographic findings of IPF. Pathogenic rare variants in multiple different genes have been described; in one FPF cohort, these explain about one-third of the kindreds. Pathogenic rare variants are found in genes encoding surfactant- and telomere-related proteins. More mutations have been found in the TERT gene, which encodes the protein component of telomerase, than any other gene. The clinical manifestations and survival characteristics of patients with pathogenic rare variants in telomere-related genes mirror those observed for certain sporadic ILD patients with short telomere lengths. Since there are so many rare variants in the human genome, determining which of these are pathogenic remains a major challenge. We discuss the evidence to support the pathogenicity of variants discovered in ILD patients, highlighting the data supporting individual TERT variants. Current practices regarding clinical and genetic testing for FPF are suggested. Because the field of pulmonary fibrosis genetics is rapidly evolving, future research may better illuminate how genetic information can be best utilized to improve the care of patients with ILD.

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Acknowledgments

The authors acknowledge helpful review by Chad Newton, John Fitzgerald, and Craig Glazer as well as support from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Traci N. Adams

  2. Department of Internal Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Columbia University Medical Center, New York, NY, USA

    Christine Kim Garcia

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  1. Traci N. Adams
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  2. Christine Kim Garcia
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Correspondence to Christine Kim Garcia .

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Editors and Affiliations

  1. Department of Internal Medicine, Section of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine & Public Health, Madison, WI, USA

    Keith C. Meyer

  2. Advanced Lung Disease and Lung Transplant Program, Inova Fairfax Hospital, Falls Church, VA, USA

    Steven D. Nathan

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Adams, T.N., Garcia, C.K. (2019). Genetics of Pulmonary Fibrosis. In: Meyer, K., Nathan, S. (eds) Idiopathic Pulmonary Fibrosis. Respiratory Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-99975-3_8

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  • DOI: https://doi.org/10.1007/978-3-319-99975-3_8

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