新型冠状病毒肺炎患者肾素 - 血管紧张素系统基因多态性及其与严重急性呼吸综合征冠状病毒2感染重症病例的关系
Renin-Angiotensin System Genes Polymorphisms in Patients With COVID-19 and Its Relation to Severe Cases of SARS-CoV-2 Infection.
作者信息
Bragina Anna E, Tarzimanova Aida I, Rodionova Yulia N, Ogibenina Ekaterina S, Suvorov Aleksandr Yu, Druzhinina Natalya A, Vasilyeva Lyubov V, Ishina Tatiana I, Medvedev Ivan D, Borlakova Marina S, Komelkova Anastasiia R, Gushchina Daria V, Khachaturov Artem A, Podzolkov Valery I
机构信息
2nd Internal Medicine (2nd Faculty Therapy) Department, N.V. Sklifosovskiy Institute of Clinical Medicine, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.
World-Class Research Center "Digital biodesign and Personalized Healthcare", Sechenov First Moscow State Medical University, Moscow, Russia.
出版信息
J Clin Med Res. 2024 Aug;16(7-8):355-362. doi: 10.14740/jocmr5223. Epub 2024 Jul 18.
BACKGROUND
Different variants of single nucleotide polymorphisms (SNPs) of angiotensinogen (AGT), angiotensin-converting enzyme type 1 (ACE1), and angiotensin II receptors type 1 (AGTR1) and 2 (AGTR2) genes determine different susceptibility to cardiovascular disease (CVD) and hypertension, which can be considered as risk factors for fatal outcomes among coronavirus disease 2019 (COVID-19) patients. The objective of our study was to assess the relation between the frequency of SNPs of the renin-angiotensin system (RAS) components, and the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
METHODS
The cross-sectional study included 100 patients with a laboratory-confirmed diagnosis of COVID-19 admitted to the hospital. Criteria for severe COVID-19 included respiratory rate (RR) > 30/min, blood oxygen saturation (SpO) ≤ 93%, signs of unstable hemodynamics with systolic blood pressure (SBP) < 90 and/or diastolic blood pressure (DBP) < 60 mm Hg. All patients were identified with alleles and genotypes of the polymorphic markers rs4762 of the AGT gene, rs1799752 of the ACE1 gene, rs5186 of the AGTR1 gene and rs1403543 of the AGTR2 gene using the polymerase chain reaction method in human DNA preparations on real-time CFX96C1000 Touch, Bio-Rad equipment (Syntol, Russia). Statistical analysis was performed in R v.4.2.
RESULTS
Patients were divided into groups with severe (n = 44) and moderate COVID-19 (n = 56). For ACE1 rs1799752, a significant deviation from the population distribution was detected in both studied subgroups. A higher frequency of the C allele SNP rs5186 AGTR1 gene was detected in the group with severe disease. More frequent A/A genotype of SNP rs1403543 AGTR2 was detected among females with severe COVID-19. Haplotype analysis revealed more common DCG haplotype among patients with severe COVID-19. The odds ratio for severe COVID-19 in the presence of the DCG haplotype was 3.996 (95% confidential interval: 1.080 -14.791, P < 0.05).
CONCLUSIONS
Our data suggest that the SNP genes of the RAS components, may allow to identify groups of patients predisposed to a more severe course of COVID-19.
背景
血管紧张素原（AGT）、血管紧张素转换酶1型（ACE1）、血管紧张素II 1型受体（AGTR1）和2型受体（AGTR2）基因的单核苷酸多态性（SNP）的不同变体决定了对心血管疾病（CVD）和高血压的不同易感性，而这可被视为2019冠状病毒病（COVID-19）患者致命结局的危险因素。我们研究的目的是评估肾素-血管紧张素系统（RAS）组分的SNP频率与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染严重程度之间的关系。
方法
这项横断面研究纳入了100例入院时实验室确诊为COVID-19的患者。重症COVID-19的标准包括呼吸频率（RR）>30次/分钟、血氧饱和度（SpO）≤93%、收缩压（SBP）<90和/或舒张压（DBP）<60 mmHg的血流动力学不稳定体征。使用实时CFX96 C1000 Touch型Bio-Rad设备（俄罗斯Syntol公司）上的人DNA制剂中的聚合酶链反应方法，对所有患者的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进行鉴定。在R v.4.2中进行统计分析。
结果
患者被分为重症（n = 44）和中度COVID-19（n = 56）组。对于ACE1 rs1799752，在两个研究亚组中均检测到与总体人群分布存在显著偏差。在重症组中检测到SNP rs5186 AGTR1基因的C等位基因频率更高。在重症COVID-19女性中检测到SNP rs1403543 AGTR2的A/A基因型更为常见。单倍型分析显示，重症COVID-19患者中DCG单倍型更为常见。存在DCG单倍型时，重症COVID-19的优势比为3.996（95%置信区间：1.080 - 14.791，P < 0.05）。
结论
我们的数据表明，RAS组分的SNP基因可能有助于识别易患更严重COVID-19病程的患者群体。
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