Bragina A E, Rodionova Y N, Ogibenina E S, Fomin A S, Podzolkov V I
Sechenov First Moscow State Medical University (Sechenov University).
Ter Arkh. 2024 Oct 10;96(9):872-878. doi: 10.26442/00403660.2024.09.202849.
Evaluation of genes polymorphisms frequencies of angiotensinogen (AGT), angiotensin converting enzyme type 1 (ACE1) and angiotensin II receptors type 1 (AGTR1) and type 2 (AGTR2) in patients admitted with coronavirus disease (COVID-19) and its association the severity of severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2).
The study included 100 patients admitted to the hospital with a laboratory-confirmed diagnosis of COVID-19. All patients were identified with alleles and genotypes of polymorphic markers rs4762 of the AGT gene, rs1799752 of the ACE1 gene, rs5186 of the AGTR1 gene and rs1403543 of the AGTR2 gene. The frequencies of each polymorphisms were compared with population. Statistical processing was performed using the Statistica 8.0 software package.
In evaluated cohort there was higher frequency of D-allele ACE1 rs1799752 compared to population. Depending on the availability of criteria for the severity of coronavirus infection, 44 (44%) patients were diagnosed with severe, 56 (56%) with moderate course. The groups did not significantly differ in age, gender, cardiovascular risk factors and comorbid pathology. In the groups with severe and moderate course, the same distribution of genotypes and alleles of AGT rs4762, AGTR2 rs1403543 and ACE1 rs1799752 was revealed. For the I/D alleles of the ACE1 rs1799752 gene, a significant deviation from the papulation was found in both the group of severe and moderate COVID-19. In the group with a severe course of the disease, a higher frequency of the mutant C-allele of the AGTR1 rs5186 gene was detected. In the same group, a deviation in the frequency ratio of A and C of the AGTR1 rs5186 alleles from Hardy-Weinberg Equilibrium was found. When calculating the risk of severe COVID-19 in the presence of the C-allele compared with the A-allele, an odds ratio 2.092 (95% confidence interval 1.066-4.108) was obtained.
The data obtained suggest that the genes polymorphisms of the components of renin-angiotensin-aldosterone system, namely D-allele of ACE1 rs1799752 and C-allele of AGTR1 rs5186, may make it possible to identify groups of patients predisposed to the development of more severe COVID-19.
评估新型冠状病毒肺炎（COVID-19）患者血管紧张素原（AGT）、血管紧张素转换酶1型（ACE1）、血管紧张素Ⅱ1型受体（AGTR1）和2型受体（AGTR2）基因多态性频率，及其与严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）感染严重程度的关联。
本研究纳入100例经实验室确诊为COVID-19的住院患者。所有患者均检测了AGT基因的多态性标记rs4762、ACE1基因的rs1799752、AGTR1基因的rs5186和AGTR2基因的rs1403543的等位基因和基因型。将各多态性的频率与总体人群进行比较。使用Statistica 8.0软件包进行统计处理。
在评估队列中，ACE1 rs1799752的D等位基因频率高于总体人群。根据冠状病毒感染严重程度的标准，44例（44%）患者被诊断为重症，56例（56%）为中症。两组在年龄、性别、心血管危险因素和合并症方面无显著差异。在重症和中症组中，AGT rs4762、AGTR2 rs1403543和ACE1 rs1799752的基因型和等位基因分布相同。对于ACE1 rs1799752基因的I/D等位基因，在重症和中症COVID-19组中均发现与总体人群有显著差异。在疾病重症组中，检测到AGTR1 rs5186基因的突变C等位基因频率较高。在同一组中，发现AGTR1 rs5186等位基因的A和C频率比偏离哈迪-温伯格平衡。在存在C等位基因与A等位基因的情况下计算重症COVID-19的风险时，获得优势比为2.092（95%置信区间1.066 - 4.108）。
所得数据表明，肾素-血管紧张素-醛固酮系统成分的基因多态性，即ACE1 rs1799752的D等位基因和AGTR1 rs5186的C等位基因，可能有助于识别易发生更严重COVID-19的患者群体。
