Targeted resequencing reveals genetic risks in patients with sporadic idiopathic pulmonary fibrosis
| Autor: | Biwen Mo, Jing Zhu, Yanyan Cao, Liman Luo, Jianghong Wei, Jingping Li, Shirong Fang, Yanhan Deng, Hua Yang, Z. Li, Ying Shu, Xuyan Xu, Renying Ge, Jingping Yang, Ming Wu, Zheng Wang, Weining Xiong, Qingzhen Peng, Xueqin Chen, Yong Mou, Bohua Fu, Zhenshun Cheng, Xiaomei Wang, Juan Liu, Yingnan Wang, Guangwei Luo, Yaqing Li, Shuo Yang, Guang Wei, Xiaoju Zhang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Oncology medicine.medical_specialty Mutation Missense Single-nucleotide polymorphism Disease Biology Polymorphism Single Nucleotide DNA sequencing 03 medical and health sciences symbols.namesake Idiopathic pulmonary fibrosis 0302 clinical medicine Risk Factors Internal medicine Receptors Colony-Stimulating Factor Genetics medicine Humans Missense mutation Genetic Predisposition to Disease In patient Gene Genetics (clinical) Sanger sequencing Genome Human High-Throughput Nucleotide Sequencing respiratory system medicine.disease Idiopathic Pulmonary Fibrosis humanities respiratory tract diseases 030104 developmental biology Desmoplakins 030228 respiratory system symbols Female Laminin Genome-Wide Association Study Signal Transduction |
| Zdroj: | Human Mutation. 39:1238-1245 |
| ISSN: | 1059-7794 |
| DOI: | 10.1002/humu.23566 |
| Popis: | Idiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. However, a large fraction of genetic cause remains unexplained, especially in sporadic IPF (∼80% IPF). By systemically reviewing related literature and potential pathogenic pathways, 92 potentially IPF-related genes were selected and sequenced in genomic DNAs from 253 sporadic IPF patients and 125 matched health controls using targeted massively parallel next-generation sequencing. The identified risk variants were confirmed by Sanger sequencing. We identified two pathogenic and 10 loss-of-function (LOF) candidate variants, accounting for 4.74% (12 out of 253) of all the IPF cases. In burden tests, rare missense variants in three genes (CSF3R, DSP, and LAMA3) were identified that have a statistically significant relationship with IPF. Four common SNPs (rs3737002, rs2296160, rs1800470, and rs35705950) were observed to be statistically associated with increased risk of IPF. In the cumulative risk model, high risk subjects had 3.47-fold (95%CI: 2.07-5.81, P = 2.34 × 10-6 ) risk of developing IPF compared with low risk subjects. We drafted a comprehensive map of genetic risks (including both rare and common candidate variants) in patients with IPF, which could provide insights to help in understanding mechanisms, providing genetic diagnosis, and predicting risk for IPF. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text