Angiotensin-converting enzymes (ACE, ACE2) gene variants and COVID-19 outcome
Angiotensin-converting enzymes (ACE, ACE2) gene variants and COVID-19 outcome
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DOI：
10.1016/j.gene.2020.145102
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发表时间：
2020-12-15
期刊：
影响因子：
3.5
通讯作者：
Coto, Eliecer
中科院分区：
文献类型：
--
作者：
Gomez, Juan;Albaiceta, Guillermo M.;Coto, Eliecer
血管紧张素系统与COVID-19的发病机制有关。首先，ACE 2是SARS-CoV-2的细胞受体，ACE 2基因的表达可以调节个体对感染的易感性。此外，ACE 1和ACE 2活性之间的平衡与呼吸道疾病的发病机制有关，并可能在COVID-19的严重程度中发挥作用。ACE 1/ACE 2基因多态性与心血管和肺部疾病的风险相关，因此也可能影响COVID-19的结局。我们研究了204例COVID-19患者（137例非重症和67例重症ICU病例）和536例年龄匹配的对照。测定ACE 1插入/缺失和ACE 2 rs 2285666多态性。通过Logistic回归分析比较各组间变量频率。我们还对一组患者的ACE 2编码核苷酸进行了测序。严重的COVID-19与高血压男性性别（p <0. 001）、高血压（p = 0. 006）、高胆固醇血症（p = 0. 046）和ACE 1-DD基因型（p = 0. 049）相关。在多元Logistic回归中，高血压（p = 0.02，OR = 2.26，95%CI = 1.12-4.63）和男性（p = 0.002，OR = 3.15，95%CI = 1.56-6.66）仍然是严重程度的独立显著预测因素。ACE 2基因多态性与疾病结局无关。ACE 2测序显示没有编码序列变异可以解释发生COVID-19的风险增加。总之，COVID-19的不良结局与男性性别、高血压、高胆固醇血症和ACE 1基因型相关。我们的研究表明，ACE 1-I/D可能影响COVID-19的严重程度，但这种影响取决于高血压状态。这一结果需要在其他大型队列中进一步验证。
The Angiotensin system is implicated in the pathogenesis of COVID-19. First, ACE2 is the cellular receptor for SARS-CoV-2, and expression of the ACE2 gene could regulate the individuals susceptibility to infection. In addition, the balance between ACE1 and ACE2 activity has been implicated in the pathogenesis of respiratory diseases and could play a role in the severity of COVID-19. Functional ACE1/ACE2 gene polymorphisms have been associated with the risk of cardiovascular and pulmonary diseases, and could thus also contribute to the outcome of COVID-19.We studied 204 COVID-19 patients (137 non-severe and 67 severe-ICU cases) and 536 age-matched controls. The ACE1 insertion/deletion and ACE2 rs2285666 polymorphism were determined. Variables frequencies were compared between the groups by logistic regression. We also sequenced the ACE2 coding nucleotides in a group of patients.Severe COVID-19 was associated with hypertension male gender (p < 0.001), hypertension (p = 0.006), hypercholesterolaemia (p = 0.046), and the ACE1-DD genotype (p = 0.049). In the multiple logistic regression hypertension (p = 0.02, OR = 2.26, 95%CI = 1.12-4.63) and male gender (p = 0.002; OR = 3.15, 95%CI = 1.56-6.66) remained as independent significant predictors of severity. The ACE2 polymorphism was not associated with the disease outcome. The ACE2 sequencing showed no coding sequence variants that could explain an increased risk of developing COVID-19.In conclusion, an adverse outcome of COVID-19 was associated with male gender, hypertension, hypercholesterolemia and the ACE1 genotype. Our work suggested that the ACE1-I/D might influence COVID-19 severity, but the effect was dependent on the hypertensive status. This result requires further validation in other large cohorts.