Respiratory Disease Unit, Department of Cardiac Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy.
University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado, USA.
Curr Opin Pulm Med. 2023 Sep 1;29(5):399-405. doi: 10.1097/MCP.0000000000000989. Epub 2023 Jul 6.
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 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.
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.
遗传学在特发性肺纤维化（IPF）易感性方面有重要作用。散发性和家族性疾病的遗传研究已经确定了几个与 IPF 相关的变异，主要涉及端粒相关和表面活性剂蛋白基因。在这里，我们回顾了关于 IPF 遗传学的最新文献，并讨论了它如何有助于疾病的发病机制。
最近的研究表明，涉及端粒维持、宿主防御、细胞生长、哺乳动物雷帕霉素靶蛋白信号、细胞-细胞黏附、TGF-β信号调节和纺锤体组装的基因与 IPF 的发病机制有关。常见和罕见的遗传变异都与 IPF 的总体风险有关；然而，虽然常见变异（即多态性）解释了散发性疾病的大部分遗传率，但罕见变异（即突变），主要在端粒相关基因中，是家族性疾病遗传率的主要贡献者。遗传因素也可能影响疾病的行为和预后。最后，最近的数据表明，IPF 与其他纤维性肺疾病共享遗传关联——可能还有一些发病机制。
常见和罕见的遗传变异与 IPF 的易感性和预后相关。然而，许多报道的变异发生在基因组的非编码区域，其与疾病病理生物学的相关性仍有待阐明。
