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作为潜在的预后和药物遗传学生物标志物的[具体基因名称1]和[具体基因名称2]的遗传变异研究:对COVID-19和神经炎症性疾病的意义。

Investigation of Genetic Variations of and as Potential Prognostic and Pharmacogenetics Biomarkers: Implications for COVID-19 and Neuroinflammatory Disorders.

作者信息

Strafella Claudia, Caputo Valerio, Termine Andrea, Barati Shila, Caltagirone Carlo, Giardina Emiliano, Cascella Raffaella

机构信息

Genomic Medicine Laboratory, IRCCS Santa Lucia Foundation, 00179 Rome, Italy.

Department of Biomedicine and Prevention, Tor Vergata University, 00133 Rome, Italy.

出版信息

Life (Basel). 2020 Dec 16;10(12):351. doi: 10.3390/life10120351.

DOI:10.3390/life10120351
PMID:33339153
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7765585/
Abstract

In the present study, we investigated the distribution of genetic variations in and genes, which may be employed as prognostic and pharmacogenetic biomarkers for COVID-19 and neurodegenerative diseases. The study was performed on 271 samples representative of the Italian general population and identified seven variants (rs140764737, rs142164099, rs2069849, rs142759801, rs190436077, rs148171375, rs13306435) in and five variants (rs2228144, rs2229237, rs2228145, rs28730735, rs143810642) within , respectively. These variants have been predicted to affect the expression and binding ability of IL6 and IL6R. Ingenuity Pathway Analysis (IPA) showed that IL6 and IL6R appeared to be implicated in several pathogenetic mechanisms associated with COVID-19 severity and mortality as well as with neurodegenerative diseases mediated by neuroinflammation. Thus, the availability of --related biomarkers for COVID-19 may be helpful to counteract harmful complications and prevent multiorgan failure. At the same time, --related biomarkers could also be useful for assessing the susceptibility and progression of neuroinflammatory disorders and undertake the most suitable treatment strategies to improve patients' prognosis and quality of life. In conclusion, this study showed how IL6 pleiotropic activity could be exploited to meet different clinical needs and realize personalized medicine protocols for chronic, age-related and modern public health emergencies.

摘要

在本研究中,我们调查了IL6和IL6R基因中遗传变异的分布情况,这些基因变异可作为COVID-19和神经退行性疾病的预后及药物遗传学生物标志物。该研究对271份代表意大利普通人群的样本进行,分别在IL6基因中鉴定出7个变异(rs140764737、rs142164099、rs2069849、rs142759801、rs190436077、rs148171375、rs13306435),在IL6R基因中鉴定出5个变异(rs2228144、rs2229237、rs2228145、rs28730735、rs143810642)。这些变异被预测会影响IL6和IL6R的表达及结合能力。通路分析(IPA)显示,IL6和IL6R似乎参与了与COVID-19严重程度和死亡率以及神经炎症介导的神经退行性疾病相关的多种致病机制。因此,获得与IL6相关的COVID-19生物标志物可能有助于对抗有害并发症并预防多器官功能衰竭。同时,与IL6相关的生物标志物也可用于评估神经炎症性疾病的易感性和进展,并采取最合适的治疗策略以改善患者的预后和生活质量。总之,本研究表明如何利用IL6的多效性活性来满足不同的临床需求,并为慢性、与年龄相关的疾病以及现代突发公共卫生事件制定个性化医疗方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6a0/7765585/2fb7dea1030d/life-10-00351-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6a0/7765585/82b5bac65787/life-10-00351-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6a0/7765585/92032c0e1ccb/life-10-00351-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6a0/7765585/2fb7dea1030d/life-10-00351-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6a0/7765585/82b5bac65787/life-10-00351-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6a0/7765585/92032c0e1ccb/life-10-00351-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6a0/7765585/2fb7dea1030d/life-10-00351-g003.jpg

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