Table_6_The Role of Angiotensin Converting Enzyme 1 Insertion/Deletion Genetic Polymorphism in the Risk and Severity of COVID-19 Infection.docx

Background: Individuals infected with the COVID-19 virus present with different symptoms of varying severity. In addition, not all individuals are infected despite exposure. Risk factors such as age, sex, and comorbidities play a major role in this variability; however, genetics may also be important in driving the differences in the incidence and prognosis of the disease. An Insertion/Deletion (I/D) polymorphism in the ACE1 gene (rs1799752) may explain these genetic differences. The aims of this study were to determine the potential role of ACE1 I/D genetic polymorphism in the risk of contracting COVID-19 as well as predicting the severity of COVID-19 infection.
Methods: Three-hundred and eighty-seven non-related Lebanese subjects, 155 controls and 232 cases, who presented to the American University of Beirut Medical Center (AUBMC) for COVID-19 PCR testing were recruited. Clinical data were collected via filling a questionnaire and accessing the medical records. Peripheral blood was withdrawn for DNA isolation, and genotyping performed with standard PCR followed by band visualization on agarose gel.
Results: In our study population, previously described risk factors such as gender, age, and comorbidities were associated with increase in disease susceptibility and severity. ACE1 I was the least common allele, and there was a positive association between ACE1 I and the risk of contracting the COVID-19 disease. More specifically, the frequency of II genotype was significantly higher among cases when compared to controls (P = 0.035) with individuals with the II genotype having greater risk for contracting the COVID-19 disease: OR = 2.074, P = 0.048 in the multivariate analysis. As for disease severity, the DD genotype and D allele were associated with increased risk for developing severe symptoms (OR = 2.845, P = 0.026 and OR = 2.359, P = 0.014, respectively), and the DD genotype with necessitating hospitalization (OR = 2.307, P = 0.042). In parallel, D allele carriers showed a significantly increased risk for developing hypoxia: OR = 4.374, P = 0.045.
Conclusion: We found a positive association between ACE1 I and the risk of contracting the COVID-19 disease, and between ACE1 D and a worse outcome of the COVID-19 infection. Therefore, genotyping for ACE1 I/D polymorphism could be used to assess risk and predict severity for better prognosis and management of the disease.

研究背景：感染新冠病毒（COVID-19）的个体所表现出的症状存在差异且严重程度各不相同；此外，部分个体虽有暴露史却并未被感染。年龄、性别、合并症等风险因素在这种差异中发挥了主要作用，但遗传因素或许也会影响疾病的发病率与预后差异。血管紧张素转换酶1（ACE1）基因的插入/缺失（Insertion/Deletion, I/D）多态性（rs1799752）或可解释这类遗传差异。本研究旨在明确ACE1基因I/D多态性在新冠病毒感染易感性以及预测新冠感染严重程度中的潜在作用。
研究方法：本研究共招募387名无亲缘关系的黎巴嫩受试者，其中155名为对照组，232名为病例组，所有受试者均前往贝鲁特美国大学医疗中心（AUBMC）接受新冠病毒聚合酶链反应（PCR）检测。研究人员通过填写问卷及查阅医疗记录收集临床数据，采集外周血以进行DNA提取，并采用标准聚合酶链反应（PCR）进行基因分型，随后通过琼脂糖凝胶电泳进行条带成像以完成基因型判读。
研究结果：在本研究的受试人群中，既往报道的性别、年龄、合并症等风险因素与疾病易感性及严重程度升高相关。ACE1基因I等位基因是最不常见的等位基因，且ACE1 I等位基因与新冠病毒感染风险呈正相关。具体而言，病例组的II基因型频率显著高于对照组（P=0.035）；多变量分析显示，携带II基因型的个体感染新冠病毒的风险更高：比值比（OR）=2.074，P=0.048。就疾病严重程度而言，DD基因型与D等位基因均与出现重症症状的风险升高相关（分别为OR=2.845, P=0.026和OR=2.359, P=0.014），且DD基因型与需住院治疗相关（OR=2.307, P=0.042）。与此同时，携带D等位基因的个体出现低氧血症的风险显著升高（OR=4.374, P=0.045）。
研究结论：本研究发现ACE1 I等位基因与新冠病毒感染风险呈正相关，而ACE1 D等位基因与新冠感染预后不良相关。因此，对ACE1 I/D多态性进行基因分型可用于评估感染风险、预测疾病严重程度，从而为新冠疾病的预后评估与临床管理提供指导。