Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Institute of Human Genetics, Jena University Hospital, 07740 Jena, Germany.
Vascul Pharmacol. 2022 Feb;142:106934. doi: 10.1016/j.vph.2021.106934. Epub 2021 Nov 10.
Contribution of the renin-angiotensinogen system in the risk of COVID-19 and related complications have been assessed by several groups. However, the results are not consistent. We examined levels of ACE1 and ACE2 in the circulation of two groups of COVID-19 patients (ICU-admitted and general ward-admitted patients) compared with healthy controls. We also genotyped two polymorphisms in ACE1 gene (the ACE1-I/D polymorphism rs1799752 and rs4359) to appraise their association with expression levels of ACE1 and ACE2. Expression level of ACE1 was significantly higher in ICU patients compared with non-ICU patients (P value = 0.02). However, its expression was not significantly different between total COVID-19 patients and total controls (P value = 0.34). ACE2 expression was not different ether between two groups of COVID-19 patients (P value = 0.12) or between total COVID-19 patients and total controls (P value = 0.79). While distribution of rs1799752 and rs4359 alleles was similar between study groups, genotype frequencies of rs1799752 were differently distributed among total COVID-19 patients and controls (P value = 0.00001). Moreover, genotypes of the other polymorphism tended to be distinctively distributed among these two groups (P value = 0.06). In the total population of patients and controls, different ACE1 mRNA levels were observed among carriers of different rs1799752 genotypes; of note, ID genotype carriers showed a higher expression of ACE1 compared with II genotype carriers (P = 0.01). ACE1 polymorphisms might affect risk of COVID-19 and expression of ACE transcripts.
肾素-血管紧张素原系统在 COVID-19 风险和相关并发症中的作用已被多个研究小组评估。然而，结果并不一致。我们检测了两组 COVID-19 患者（入住 ICU 患者和普通病房患者）与健康对照者循环中的 ACE1 和 ACE2 水平。我们还对 ACE1 基因的两个多态性（ACE1-I/D 多态性 rs1799752 和 rs4359）进行了基因分型，以评估它们与 ACE1 和 ACE2 表达水平的关系。与非 ICU 患者相比，ICU 患者的 ACE1 表达水平显著升高（P 值=0.02）。然而，在 COVID-19 患者和对照组之间，ACE1 的表达没有显著差异（P 值=0.34）。ACE2 的表达在两组 COVID-19 患者之间（P 值=0.12）或在 COVID-19 患者和对照组之间（P 值=0.79）也没有差异。虽然 ACE1 基因 rs1799752 和 rs4359 等位基因的分布在研究组之间相似，但 rs1799752 的基因型频率在 COVID-19 患者和对照组之间的分布不同（P 值=0.00001）。此外，另一个多态性的基因型在这两组之间也有明显的分布差异（P 值=0.06）。在患者和对照组的总人群中，不同 rs1799752 基因型的 ACE1 mRNA 水平不同；值得注意的是，ID 基因型携带者的 ACE1 表达高于 II 基因型携带者（P=0.01）。ACE1 多态性可能影响 COVID-19 的风险和 ACE 转录物的表达。
