背景:血管紧张素转换酶2(ACE2)是肾素-血管紧张素系统(RAS)的关键组成部分,对其影响进行反监管,同时,SARS-CoV-2进入的受体。建议调节RAS主要成分平衡的因素,包括ACE2基因多态性,RAS阻滞剂(ACE抑制剂和血管紧张素受体阻滞剂)治疗可能会影响COVID-19的严重程度。
目的:本研究的目的是研究RAS成分的作用,ACE2基因多态性rs2106809和ACEi/ARBs治疗与COVID-19严重程度的关系。
方法:该研究包括在内分泌学研究中心住院的COVID-19患者(n=173),他们被分为中度和重度两组。通过ELISA进行RAS成分的测定,通过PCR鉴定多态性。使用非参数统计方法进行统计分析;使用Fisher精确检验χ2评估基因型频率分布的差异。
结果:各组在年龄上有显著差异,血糖水平,和炎症标志物:白细胞,中性粒细胞,IL-6,D-二聚体,C反应蛋白,铁蛋白和肝酶,这与疾病的严重程度有关。当比较患者的ACE时,ACE2,血管紧张素II,ADAM17组间差异无统计学意义(分别为p=0.544,p=0.054,p=0.836,p=1.0),包括性别分布(男性:p=0.695,p=0.726,p=0.824,p=0.512;女性:p=0.873,p=0.196,p=0.150,p=0.937)。分析AA的分布,AG,ACE2基因rs2106809多态性的GG基因型也显示患者之间没有差异:男性中χ21.35,p=0.071,女性χ25.28,p=0.244。不同病程严重程度组使用RAS阻滞剂的差异无统计学意义:ACEi的χ20.208,p=0.648,ARBs的χ21.15,p=0.283。
结论:在我们的研究中,RAS成分激活的影响(ACE,ACE2,ATII,ADAM17)和ACE2基因多态性对COVID-19病程的严重程度未证实。COVID-19病程的严重程度与标准炎症标志物水平相关,表明感染作为全身性炎症的一般原则,无论RAS的遗传和功能状态如何。
Angiotensin-converting enzyme 2 (ACE2) is a key component of the renin-angiotensin system (RAS), providing counter-regulation of its effects and, simultaneously, a receptor for the SARS-CoV-2 entering. It is suggested that factors regulating the balance of the major components of RAS, including ACE2 gene polymorphism, therapy with RAS blockers (ACE inhibitors and angiotensin receptor blockers) - may affect the severity of COVID-19.
The aim of the study was to investigate the effect of RAS components, the relationship of ACE2 gene polymorphism rs2106809 and ACEi/ARBs therapy with the COVID-19 severity.
The study included patients with COVID-19 hospitalized in Endocrinology research centre (n = 173), who were divided into groups of moderate and severe course. Determination of RAS components was performed by ELISA, identification of polymorphism by PCR. Statistical analysis was performed using nonparametric statistical methods; differences in the distribution of genotype frequencies were assessed using Fisher\'s exact test χ2.
The groups differed significantly in age, blood glucose levels, and inflammatory markers: leukocytes, neutrophils, IL-6, D-dimer, C-reactive protein, ferritin and liver enzymes, which correlated with the severity of the disease. When comparing patients in terms of ACE, ACE2, angiotensin II, ADAM17 there were no statistically significant differences between the groups (p=0.544, p=0.054, p=0.836, p=1.0, respectively), including the distribution by gender (in men: p=0.695, p=0.726, p=0.824, p=0.512; in women: p=0.873, p=0.196, p=0.150, p=0.937). Analysis of the distribution of AA, AG, and GG genotypes of the rs2106809 polymorphism of the ACE2 gene also revealed no differences between patients: χ2 1.35, p=0.071 in men, χ2 5.28, p=0.244 in women. There were no significant differences in the use of RAS blockers between groups with different course severity: χ2 0.208, p=0.648 for ACEi, χ2 1.15, p=0.283 for ARBs.
In our study, the influence of activation of RAS components (ACE, ACE2, AT II, ADAM17) and ACE2 gene polymorphism on the severity of COVID-19 course was not confirmed. The severity of COVID-19 course correlated with the level of standard inflammatory markers, indicating the general principles of the infection as a systemic inflammation, regardless of the genetic and functional status of the RAS.