Infectious Diseases Unit, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy.
Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD 20892, USA.
Viruses. 2023 Jun 27;15(7):1448. doi: 10.3390/v15071448.
The novel SARS-CoV-2 coronavirus causes a severe respiratory syndrome referred to as coronavirus disease (COVID-19). The angiotensin-converting enzyme 2 (ACE-2) plays an important role as a cellular receptor for SARS-CoV-2 and is largely expressed in lungs, kidneys, heart and the gastrointestinal tract along with being shed in plasma. The ACE-2 gene and protein show a high level of genetic polymorphism, including simple nucleotide variation, transcriptional variation, post-transcriptional changes, and putative protein mutations that could interfere with the binding or entry of SARS-CoV-2 and affect tissue damage in lungs or other organs. Genetic polymorphisms can impact SARS-CoV-2 viral entry and COVID-19 severity. This single-center study evaluated the possible role of the main ACE-2 polymorphisms (rs143936283, rs2285666, rs41303171, rs35803318, and rs2106809) as potential prognostic markers in SARS-CoV-2-infected individuals. Frozen whole blood was used for DNA isolation and genomic DNA samples were sheared using the Covaris LE220 Focused-ultrasonicator for targeting a peak size of 410 bp. Whole-genome sequencing libraries were generated from fragmented DNA using the Illumina TruSeq DNA PCR-Free HT Library Preparation Kit and sequenced on an Illumina NovaSeq 6000. We did not identify any correlation between ACE-2 polymorphisms and COVID-19 prognosis, suggesting that the interpretation and clinical use of ACE-2 genetic polymorphisms in real-world clinical settings requires further experimental and clinical validation.
新型严重急性呼吸综合征冠状病毒 2 引发的严重呼吸道综合征被称为冠状病毒病（COVID-19）。血管紧张素转换酶 2（ACE-2）作为 SARS-CoV-2 的细胞受体发挥着重要作用，在肺、肾、心脏和胃肠道中大量表达，并在血浆中释放。ACE-2 基因和蛋白表现出高水平的遗传多态性，包括单核苷酸变异、转录变异、转录后变化和可能的蛋白突变，这些可能会干扰 SARS-CoV-2 的结合或进入，并影响肺部或其他器官的组织损伤。遗传多态性会影响 SARS-CoV-2 病毒进入和 COVID-19 的严重程度。这项单中心研究评估了主要 ACE-2 多态性（rs143936283、rs2285666、rs41303171、rs35803318 和 rs2106809）作为 SARS-CoV-2 感染个体潜在预后标志物的可能作用。使用冰冻全血分离 DNA，并用 Covaris LE220 聚焦式超声破碎仪将基因组 DNA 样本破碎，以达到 410bp 的峰值大小。使用 Illumina TruSeq DNA PCR-Free HT 文库制备试剂盒从片段化 DNA 生成全基因组测序文库，并在 Illumina NovaSeq 6000 上进行测序。我们没有发现 ACE-2 多态性与 COVID-19 预后之间存在任何相关性，这表明 ACE-2 遗传多态性在真实临床环境中的解释和临床应用需要进一步的实验和临床验证。
