Idiopathic pulmonary fibrosis and the role of genetics in the era of precision medicine
Idiopathic pulmonary fibrosis (IPF) is a chronic, rare progressive lung disease, characterized by lung scarring and the irreversible loss of lung function. Two anti-fibrotic drugs, nintedanib and pirfenidone, have been demonstrated to slow down disease progression, although IPF mortality remains a c...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2023.1152211/full |
| _version_ | 1797838612699545600 |
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| author | Aitana Alonso-Gonzalez Aitana Alonso-Gonzalez Eva Tosco-Herrera Maria Molina-Molina Maria Molina-Molina Maria Molina-Molina Carlos Flores Carlos Flores Carlos Flores Carlos Flores |
| author_facet | Aitana Alonso-Gonzalez Aitana Alonso-Gonzalez Eva Tosco-Herrera Maria Molina-Molina Maria Molina-Molina Maria Molina-Molina Carlos Flores Carlos Flores Carlos Flores Carlos Flores |
| author_sort | Aitana Alonso-Gonzalez |
| collection | DOAJ |
| description | Idiopathic pulmonary fibrosis (IPF) is a chronic, rare progressive lung disease, characterized by lung scarring and the irreversible loss of lung function. Two anti-fibrotic drugs, nintedanib and pirfenidone, have been demonstrated to slow down disease progression, although IPF mortality remains a challenge and the patients die after a few years from diagnosis. Rare pathogenic variants in genes that are involved in the surfactant metabolism and telomere maintenance, among others, have a high penetrance and tend to co-segregate with the disease in families. Common recurrent variants in the population with modest effect sizes have been also associated with the disease risk and progression. Genome-wide association studies (GWAS) support at least 23 genetic risk loci, linking the disease pathogenesis with unexpected molecular pathways including cellular adhesion and signaling, wound healing, barrier function, airway clearance, and innate immunity and host defense, besides the surfactant metabolism and telomere biology. As the cost of high-throughput genomic technologies continuously decreases and new technologies and approaches arise, their widespread use by clinicians and researchers is efficiently contributing to a better understanding of the pathogenesis of progressive pulmonary fibrosis. Here we provide an overview of the genetic factors known to be involved in IPF pathogenesis and discuss how they will continue to further advance in this field. We also discuss how genomic technologies could help to further improve IPF diagnosis and prognosis as well as for assessing genetic risk in unaffected relatives. The development and validation of evidence-based guidelines for genetic-based screening of IPF will allow redefining and classifying this disease relying on molecular characteristics and contribute to the implementation of precision medicine approaches. |
| first_indexed | 2024-04-09T15:44:47Z |
| format | Article |
| id | doaj.art-f602b37548cb4413b6512dd7fdc51724 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-09T15:44:47Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-f602b37548cb4413b6512dd7fdc517242023-04-27T05:31:30ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-04-011010.3389/fmed.2023.11522111152211Idiopathic pulmonary fibrosis and the role of genetics in the era of precision medicineAitana Alonso-Gonzalez0Aitana Alonso-Gonzalez1Eva Tosco-Herrera2Maria Molina-Molina3Maria Molina-Molina4Maria Molina-Molina5Carlos Flores6Carlos Flores7Carlos Flores8Carlos Flores9Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, SpainUniversidad de Santiago de Compostela, Santiago de Compostela, SpainUnidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, SpainServei de Pneumologia, Laboratori de Pneumologia Experimental, IDIBELL, Barcelona, SpainCampus de Bellvitge, Universitat de Barcelona, Barcelona, SpainCIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, SpainUnidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, SpainCIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, SpainGenomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerife, SpainFacultad de Ciencias de la Salud, Universidad Fernando Pessoa Canarias, Las Palmas de Gran Canaria, SpainIdiopathic pulmonary fibrosis (IPF) is a chronic, rare progressive lung disease, characterized by lung scarring and the irreversible loss of lung function. Two anti-fibrotic drugs, nintedanib and pirfenidone, have been demonstrated to slow down disease progression, although IPF mortality remains a challenge and the patients die after a few years from diagnosis. Rare pathogenic variants in genes that are involved in the surfactant metabolism and telomere maintenance, among others, have a high penetrance and tend to co-segregate with the disease in families. Common recurrent variants in the population with modest effect sizes have been also associated with the disease risk and progression. Genome-wide association studies (GWAS) support at least 23 genetic risk loci, linking the disease pathogenesis with unexpected molecular pathways including cellular adhesion and signaling, wound healing, barrier function, airway clearance, and innate immunity and host defense, besides the surfactant metabolism and telomere biology. As the cost of high-throughput genomic technologies continuously decreases and new technologies and approaches arise, their widespread use by clinicians and researchers is efficiently contributing to a better understanding of the pathogenesis of progressive pulmonary fibrosis. Here we provide an overview of the genetic factors known to be involved in IPF pathogenesis and discuss how they will continue to further advance in this field. We also discuss how genomic technologies could help to further improve IPF diagnosis and prognosis as well as for assessing genetic risk in unaffected relatives. The development and validation of evidence-based guidelines for genetic-based screening of IPF will allow redefining and classifying this disease relying on molecular characteristics and contribute to the implementation of precision medicine approaches.https://www.frontiersin.org/articles/10.3389/fmed.2023.1152211/fullIdiopathic pulmonary fibrosisgenetic testingprecision medicineexome sequencingtelomere length |
| spellingShingle | Aitana Alonso-Gonzalez Aitana Alonso-Gonzalez Eva Tosco-Herrera Maria Molina-Molina Maria Molina-Molina Maria Molina-Molina Carlos Flores Carlos Flores Carlos Flores Carlos Flores Idiopathic pulmonary fibrosis and the role of genetics in the era of precision medicine Frontiers in Medicine Idiopathic pulmonary fibrosis genetic testing precision medicine exome sequencing telomere length |
| title | Idiopathic pulmonary fibrosis and the role of genetics in the era of precision medicine |
| title_full | Idiopathic pulmonary fibrosis and the role of genetics in the era of precision medicine |
| title_fullStr | Idiopathic pulmonary fibrosis and the role of genetics in the era of precision medicine |
| title_full_unstemmed | Idiopathic pulmonary fibrosis and the role of genetics in the era of precision medicine |
| title_short | Idiopathic pulmonary fibrosis and the role of genetics in the era of precision medicine |
| title_sort | idiopathic pulmonary fibrosis and the role of genetics in the era of precision medicine |
| topic | Idiopathic pulmonary fibrosis genetic testing precision medicine exome sequencing telomere length |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2023.1152211/full |
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