单核苷酸多态性
精密医学
医学
SNP公司
特发性肺纤维化
疾病
基因检测
生物信息学
个性化医疗
基因组学
肺纤维化
人类遗传学
遗传学
生物
基因
病理
纤维化
基因型
肺
基因组
内科学
作者
Ayodeji Adegunsoye,Jonathan A. Kropski,Jürgen Behr,Timothy S. Blackwell,Tamera J. Corte,Vincent Cottin,Allan R. Glanville,Marilyn K. Glassberg,Matthias Griese,Gary M. Hunninghake,Kerri A. Johannson,Michael P. Keane,John S. Kim,Martin Kolb,Toby M. Maher,Justin M. Oldham,Anna J. Podolanczuk,Iván O. Rosas,Fernando J. Martínez,Imre Noth,David A. Schwartz
标识
DOI:10.1164/rccm.202401-0238so
摘要
Recent genetic and genomic advancements have elucidated the complex etiology of idiopathic pulmonary fibrosis (IPF) and other progressive fibrotic interstitial lung diseases (ILDs), emphasizing the contribution of heritable factors. This state-of-the-art review synthesizes evidence on significant genetic contributors to pulmonary fibrosis (PF), including rare genetic variants and common single nucleotide polymorphisms (SNPs). The MUC5B promoter variant is unusual, a common SNP that markedly elevates the risk of early and established PF. We address the utility of genetic variation in enhancing understanding of disease pathogenesis, clinical phenotypes, improving disease definitions, and informing prognosis and treatment response. Critical research gaps are highlighted, particularly the underrepresentation of non-European ancestries in PF genetic studies and the exploration of PF phenotypes beyond usual interstitial pneumonia (UIP)/IPF. We discuss the role of telomere length, often critically short in PF, and its link to progression and mortality, underscoring the genetic complexity involving telomere biology genes (TERT, TERC) and others like SFTPC and MUC5B. Additionally, we address the potential of gene-by-environment interactions to modulate disease manifestation, advocating for precision medicine in PF. Insights from gene expression profiling studies and multi-omic analyses highlight the promise for understanding disease pathogenesis and offer new approaches to clinical care, therapeutic drug development, and biomarker discovery. Finally, we discuss the ethical, legal, and social implications of genomic research and therapies in PF, stressing the need for sound practices and informed clinical genetic discussions. Looking forward, we advocate for comprehensive genetic testing panels and polygenic risk scores to improve the management of PF and related ILDs across diverse populations.
科研通智能强力驱动
Strongly Powered by AbleSci AI