Lung expression of genes putatively involved in SARS-CoV-2 infection is modulated in cis by germline variants.
Lung expression of genes putatively involved in SARS-CoV-2 infection is modulated in cis by germline variants.
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与SARS-CoV-2感染相关的肺内基因表达受种系变异体顺式调节
DOI：
10.1038/s41431-021-00831-y
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Colombo F
中科院分区：
文献类型：
--
作者：
Cotroneo CE;Mangano N;Dragani TA;Colombo F
参与SARS-CoV-2细胞进入和宿主对病毒的先天免疫反应的基因的种系变异可能影响感染的易感性。本研究利用肺组织的全基因组分析来鉴定作为表达数量性状位点（eQTL）的60个与SARS-CoV-2感染易感性相关的基因的多态性。在408例肺腺癌患者的非病变肺组织中研究了在病毒进入复制和宿主抗病毒反应中具有确认或可能作用的基因的表达。没有基因的表达因性别而异，但APOBEC 3 H水平较高，PARP 12水平较低。共检测到125个cis-eQTLs（假发现率< 0.05）调控15个基因（ABO、ANPEP、AP 2A 2、APOBEC 3D、APOBEC 3G、BSG、CLEC 4G、DDX 58、DPP 4、FURIN、FYCO 1、RAB 14、SERINC 3、TRIM 5、ZCRB 1）的mRNA表达。在COVID-19易感基因座中发现了调控ABO和FYCO 1的eQTL。未发现trans-eQTL。这15个基因编码假定的病毒受体、囊泡运输所需的蛋白质、干扰病毒复制的酶和其他限制因子，它们的表达受到遗传控制，这可能是SARS-CoV-2或其他病毒感染风险或严重程度的个体间差异的基础。
Germline variants in genes involved in SARS-CoV-2 cell entry and in host innate immune responses to viruses may influence the susceptibility to infection. This study used whole-genome analyses of lung tissue to identify polymorphisms acting as expression quantitative trait loci (eQTLs) for 60 genes of relevance to SARS-CoV-2 infection susceptibility. The expression of genes with confirmed or possible roles in viral entry–replication and in host antiviral responses was studied in the non-diseased lung tissue of 408 lung adenocarcinoma patients. No gene was differently expressed by sex, but APOBEC3H levels were higher and PARP12 levels lower in older individuals. A total of 125 cis-eQTLs (false discovery rate < 0.05) was found to modulate mRNA expression of 15 genes (ABO, ANPEP, AP2A2, APOBEC3D, APOBEC3G, BSG, CLEC4G, DDX58, DPP4, FURIN, FYCO1, RAB14, SERINC3, TRIM5, ZCRB1). eQTLs regulating ABO and FYCO1 were found in COVID-19 susceptibility loci. No trans-eQTLs were identified. Genetic control of the expression of these 15 genes, which encode putative virus receptors, proteins required for vesicle trafficking, enzymes that interfere with viral replication, and other restriction factors, may underlie interindividual differences in risk or severity of infection with SARS-CoV-2 or other viruses.
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影响因子：
5.6
作者：
Li, Jinhui;Chen, Yan;Li, Ming;Carpenter, Michael A.;McDougle, Rebecca M.;Luengas, Elizabeth M.;Macdonald, Patrick J.;Harris, Reuben S.;Mueller, Joachim D.
通讯作者：
Mueller, Joachim D.
影响因子：
4.6
作者：
Milewska A;Kindler E;Vkovski P;Zeglen S;Ochman M;Thiel V;Rajfur Z;Pyrc K
通讯作者：
Pyrc K
DOI：
10.1016/j.bbrc.2004.08.208
发表时间：
2004-10-22
影响因子：
3.1
作者：
Itoyama, S;Keicho, N;Sasazuki, T
通讯作者：
Sasazuki, T
影响因子：
5.4
作者：
Harari, Ariana;Ooms, Marcel;Simon, Viviana
通讯作者：
Simon, Viviana
影响因子：
64.8
作者：
Everitt, Aaron R.;Clare, Simon;Pertel, Thomas;John, Sinu P.;Wash, Rachael S.;Smith, Sarah E.;Chin, Christopher R.;Feeley, Eric M.;Sims, Jennifer S.;Adams, David J.;Wise, Helen M.;Kane, Leanne;Goulding, David;Digard, Paul;Anttila, Verneri;Baillie, J. Kenneth;Walsh, Tim S.;Hume, David A.;Palotie, Aarno;Xue, Yali;Colonna, Vincenza;Tyler-Smith, Chris;Dunning, Jake;Gordon, Stephen B.;Smyth, Rosalind L.;Openshaw, Peter J.;Dougan, Gordon;Brass, Abraham L.;Kellam, Paul
通讯作者：
Kellam, Paul