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Targeted resequencing reveals genetic risks in patients with sporadic idiopathic pulmonary fibrosis

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单位: [1]Huazhong Univ Sci & Technol,Tongji Hosp,Dept Resp & Crit Care Med,Key Lab Pulm Dis,Hlth M,Tongji Med Coll,Key Cite Natl Clin Res Ctr Resp D,Wuhan 430030,Hubei,Peoples R China [2]Huazhong Univ Sci & Technol,Tongji Hosp,Div Cardiol,Dept Internal Med,Tongji Med Coll,Wuhan,Hubei,Peoples R China [3]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Genet Diagnosis Ctr,Wuhan,Hubei,Peoples R China [4]Zhengzhou Univ, Dept Resp Med, Henan Prov Peoples Hosp, Zhengzhou 450003, Henan, Peoples R China [5]Zhengzhou Univ, Peoples Hosp, Zhengzhou 450003, Henan, Peoples R China [6]Guilin Med Univ, Dept Resp Med, Affiliated Hosp, Guilin, Peoples R China [7]Wuhan Univ, Dept Resp Med, Zhongnan Hosp, Wuhan, Hubei, Peoples R China [8]Peoples Liberat Army, Dept Pediat, Hosp 306, Beijing, Peoples R China [9]Qianjiang Cent Hosp, Dept Resp Med, Qianjiang, Peoples R China [10]Army Med Univ, Southwest Hosp, Dept Geriatr, Chongqing, Peoples R China [11]Wuhan 1 Hosp, Dept Resp Med, Wuhan, Hubei, Peoples R China [12]Three Gorges Univ, Dept Resp & Crit Care Med, Renmin Hosp, Yichang, Peoples R China [13]Inner Mongolia Med Univ, Affiliated Hosp 3, Dept Resp & Crit Care Med, Baotou, Peoples R China [14]Hubei Univ Sci & Technol, Affiliated Hosp 1, Dept Resp Med, Xianning Ctr Hosp, Xianning, Peoples R China [15]Wuhan Univ, Renmin Hosp, Dept Resp & Crit Care Med, Wuhan, Hubei, Peoples R China [16]Xiaogan Cent Hosp, Dept Resp Med, Xiaogan, Peoples R China [17]Zhejiang Prov Peoples Hosp, Dept Resp Med, Hangzhou, Zhejiang, Peoples R China [18]Hubei Univ Nationalities, Dept Resp Med, Univ Hosp, Enshi, Peoples R China
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关键词: common SNP genetic factors idiopathic pulmonary fibrosis next-generation sequencing risk stratification

摘要:
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 (similar to 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 x 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.

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出版当年[2017]版:
大类 | 2 区 医学
小类 | 2 区 遗传学
最新[2025]版:
大类 | 2 区 医学
小类 | 2 区 遗传学
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出版当年[2016]版:
Q1 GENETICS & HEREDITY
最新[2023]版:
Q2 GENETICS & HEREDITY

影响因子: 最新[2023版] 最新五年平均 出版当年[2016版] 出版当年五年平均 出版前一年[2015版] 出版后一年[2017版]

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第一作者单位: [1]Huazhong Univ Sci & Technol,Tongji Hosp,Dept Resp & Crit Care Med,Key Lab Pulm Dis,Hlth M,Tongji Med Coll,Key Cite Natl Clin Res Ctr Resp D,Wuhan 430030,Hubei,Peoples R China
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通讯机构: [4]Zhengzhou Univ, Dept Resp Med, Henan Prov Peoples Hosp, Zhengzhou 450003, Henan, Peoples R China [5]Zhengzhou Univ, Peoples Hosp, Zhengzhou 450003, Henan, Peoples R China
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