THE MUC5B PROMOTOR POLYMORPHISM ASSOCIATES WITH SEVERE COVID-19
THE MUC5B PROMOTOR POLYMORPHISM ASSOCIATES WITH SEVERE COVID-19
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MUC5B 启动子多态性与严重的 COVID-19 相关
DOI：
10.1101/2020.05.12.20099333
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
J. Grutters
中科院分区：
文献类型：
--
作者：
C. V. van Moorsel;J. J. van der Vis;C. Benschop;H. Ruven;M. Quanjel;J. Grutters
对暴露于严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）的反应的多样性是常见的，可能与先天免疫反应有关。粘蛋白MUC5B是先天免疫应答的重要组成部分，其表达水平与MUC5B启动子多态性rs35705950相关。rs35705950的高表达t等位基因是一种被称为特发性肺纤维化（IPF）的非感染性衰老肺部疾病的公认风险等位基因。然而，鉴于衰老肺部疾病的权衡理论和高表达对充分免疫反应的重要性，我们假设t等位基因对2019年严重冠状病毒病（COVID-19）具有保护作用。方法收集荷兰圣安东尼奥医院108例因COVID-19住院的患者的人口统计学、放射学、生存数据和MUC5B rs35705950等位基因状态。为了与白人对照队列比较等位基因频率和等位基因携带情况，将患者队列分为白人（n=83）和非白人队列。结果患者中位年龄66岁，男性居多（74%），死亡23例（21%）。白人患者rs35705950的t等位基因频率为0.04，显著低于白人对照的0.10，差异有统计学意义（p= 0.02）。此外，比较T等位基因携带者和非携带者的数量，只有8.4%的患者携带T等位基因，而对照组为18% （p=0.029； OR= 0.41， CI=0.19-0.94）。结论MUC5B rs35705950启动子多态性与COVID-19相关。IPF的风险等位基因(T)对COVID-19严重疾病的发展具有保护作用。这是呼吸系统中与衰老疾病相关的最佳表达水平之间权衡的又一个例子。然而，这些结果需要进一步调查。
Background Diversity in response to exposition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is common and may be related to the innate immune response. The mucin MUC5B is an important component of the innate immune response and expression levels are associated with the MUC5B promoter polymorphism, rs35705950. The high expressing T-allele of rs35705950 is an accepted risk allele for a non-infectious aging lung disease called idiopathic pulmonary fibrosis (IPF). However, given the theory of trade-offs in aging lung disease and the importance of high expression for an adequate immune response, we hypothesize that the T-allele is protective against severe coronavirus disease 2019 (COVID-19). Methods We collected demographics, radiology, survival data and MUC5B rs35705950 allele status for 108 patients requiring hospitalisation for COVID-19 at St Antonius Hospital in The Netherlands. For comparison of allele frequencies and allele carriership with a white control cohort, the patient cohort was divided in a white (n=83) and non-white cohort. Results The patients had a median age of 66 years and consisted predominantly of males (74%) and 23 patients (21%) died. The T-allele frequencies of rs35705950 in white patients was 0.04 which was significantly lower than the T-allele frequency of 0.10 in white controls (p= 0.02). Moreover, comparison of the number of carriers and non-carriers of the T allele showed that only 8.4% of patients carried the T-allele versus 18% of controls (p=0.029; OR= 0.41, CI=0.19-0.94). Conclusions The MUC5B rs35705950 promoter polymorphism associates with COVID-19. The risk allele (T) for IPF is protective against the development of severe COVID-19 disease. This is a further example of a trade-off between optimal expression levels in the respiratory system which associates with aging diseases. However, these results require further investigation.
DOI：
10.1172/jci15217
发表时间：
2002-03
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
M. Knowles;R. Boucher
通讯作者：
M. Knowles;R. Boucher
DOI：
10.1001/jama.2013.5827
发表时间：
2013-06-05
期刊：
JAMA
影响因子：
--
作者：
Peljto AL;Zhang Y;Fingerlin TE;Ma SF;Garcia JG;Richards TJ;Silveira LJ;Lindell KO;Steele MP;Loyd JE;Gibson KF;Seibold MA;Brown KK;Talbert JL;Markin C;Kossen K;Seiwert SD;Murphy E;Noth I;Schwarz MI;Kaminski N;Schwartz DA
通讯作者：
Schwartz DA
DOI：
10.1164/rccm.201403-0541oc
发表时间：
2014-10-15
影响因子：
24.7
作者：
Molyneaux, Phillip L.;Cox, Michael J.;Moffatt, Miriam F.
通讯作者：
Moffatt, Miriam F.