ATG7中的功能变异rs2122031与放射性肺炎的风险相关

IF 5.9 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Bo Liu, Yulong Yu, Wan Qin, Li Yang, Minxiao Yi, Lingyan Xiao, Yongbiao Huang, Xiao Zhou, Shiying Yu, Yihua Wang, Cong-Yi Wang, Yang Tang, Xianglin Yuan
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引用次数: 0

摘要

放射性肺炎(RP)以炎症为特征,并伴有自噬。然而,自噬相关基因的功能遗传变异与放射性肺炎之间的关系尚不清楚。在这项研究中,我们旨在研究参与自噬的基因的遗传变异是否与放射性肺炎有关。采用MassArray和Sanger测序技术对301例患者自噬通路5个基因的13个单核苷酸多态性(snp)进行基因分型。两名放射肿瘤学家分别通过胸部x光片或CT测量了RP的程度。多因素Cox风险分析和多重检验显示,ATG7: rs2122031 GA/GG显著降低RP≥3级的风险(HR=0.369, 95% CI: 0.189 ~ 0.720, P=0.003, Pc=0.039)。此外,qRT-PCR和免疫组织化学分析表明ATG7: rs2122031 AA基因型与ATG7表达降低有关。在成纤维细胞或条件ATG7敲除小鼠中,ATG7缺失导致的自噬丧失被证明会增加放射性肺炎。单细胞RNA-seq揭示辐照应激后ATG7基因敲除小鼠自噬相关基因的富集调控。我们的研究结果表明,ATG7的遗传变异与RP相关,因此可以在放疗前预测RP。ATG7的缺失也被证明促进RP,这表明ATG7可能是RP的干预靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A Functional Variant rs2122031 in ATG7 Is Associated with the Risk of Radiation Pneumonitis.

Radiation pneumonitis (RP) is characterized by inflammation and is associated with autophagy. However, the relationship between functional genetic variants of autophagy-related genes and radiation pneumonitis remains unknow. In this study we aimed to investigate whether genetic variants of genes involved in autophagy are associated with radiation pneumonitis. Genotyping was conducted on a total of 301 patients for thirteen single nucleotide polymorphisms (SNPs) of 5 genes in the autophagy pathway using MassArray and Sanger sequencing. Two radiation oncologists independently measured the degree of RP by chest X-ray or CT. The multivariate Cox hazard analysis and multiple testing showed that ATG7: rs2122031 GA/GG significantly decreased the risk of RP ≥ grade 3 (HR=0.369, 95% CI: 0.189-0.720, P=0.003, Pc=0.039). Furthermore, qRT-PCR and immunohistochemical analysis demonstrated that the ATG7: rs2122031 AA genotypes were related to decreased expression of ATG7. Loss of autophagy by deletion of ATG7 in fibroblasts or conditional ATG7 knockout mice was proven to increase radiation pneumonitis. Single-cell RNA-seq revealed regulation of autophagy related genes enriched after irradiation stress in conditional ATG7 knockout mice. Our findings indicated that genetic variants of ATG7 were associated with RP and may therefore be used to predict RP before radiotherapy. Loss of ATG7 was also shown to promote RP, which suggested that ATG7 may be an intervention target for RP. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

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来源期刊
CiteScore
11.20
自引率
3.10%
发文量
370
审稿时长
3-8 weeks
期刊介绍: The American Journal of Respiratory Cell and Molecular Biology publishes papers that report significant and original observations in the area of pulmonary biology. The focus of the Journal includes, but is not limited to, cellular, biochemical, molecular, developmental, genetic, and immunologic studies of lung cells and molecules.
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