Recent advances in the genetics of idiopathic pulmonary fibrosis

Abstract

Purpose of review: Genetics contributes substantially to the susceptibility to idiopathic pulmonary fibrosis (IPF). Genetic studies in sporadic and familial disease have identified several IPF-associated variants, mainly in telomere-related and surfactant protein genes.Here, we review the most recent literature on genetics of IPF and discuss how it may contribute to disease pathogenesis.

Recent findings: Recent studies implicate genes involved in telomere maintenance, host defence, cell growth, mammalian target of rapamycin signalling, cell-cell adhesion, regulation of TGF-β signalling and spindle assembly as biological processes involved in the pathogenesis of IPF. Both common and rare genetic variants contribute to the overall risk of IPF; however, while common variants (i.e. polymorphisms) account for most of the heritability of sporadic disease, rare variants (i.e. mutations), mainly in telomere-related genes, are the main contributors to the heritability of familial disease. Genetic factors are likely to also influence disease behaviour and prognosis. Finally, recent data suggest that IPF shares genetic associations - and probably some pathogenetic mechanisms - with other fibrotic lung diseases.

Summary: Common and rare genetic variants are associated with susceptibility and prognosis of IPF. However, many of the reported variants fall in noncoding regions of the genome and their relevance to disease pathobiology remains to be elucidated.

Box 1

no caption available

FIGURE 1

A 41-year-old man with familial pulmonary fibrosis listed for lung transplantation. High-resolution computed tomography shows ground glass opacity (continuous arrows), and paraseptal emphysema (dashed arrows). Both abnormalities predominate in the upper zones. This patient was found to carry a heterozygous TERC mutation.