Department of Pharmacology & Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.
Virol J. 2022 Mar 19;19(1):48. doi: 10.1186/s12985-022-01782-6.
COVID-19 and the renin-angiotensin system (RAS) are linked by angiotensin-converting enzyme 2 (ACE2), a key enzyme in RAS that has been validated as a SARS-CoV-2 receptor. Functional ACE1/ACE2 gene polymorphisms may lead to the imbalance between ACE/ACE2 ratio and thus generating RAS imbalance that is associated with higher degrees of lung damage in ARDS that may contribute to the COVID-19 infection outcome. Herein, we investigated the role of RAS gene polymorphisms, ACE1 (A2350G) and ACE2 (G8790A) as risk predictors for susceptibility and severity of COVID-19 infection. A total of 129 included: negative controls without a history of COVID-19 infection (n = 50), positive controls with a history of COVID-19 infection who were not hospitalized (n = 35), and patients with severe COVID-19 infection who were hospitalized in the intensive care unit (n = 44). rs4343 of ACE and rs2285666 of ACE2 were genotyped using PCR-RFLP method. Our results indicated that susceptibility to COVID-19 infection was associated with age, GG genotype of A2350G (Pa = 0.01; OR 4.7; 95% CI 1.4-15.1 and Pc = 0.040; OR 2.5; 95% CI 1.05-6.3) and GG genotype of G8790A (Pa = 0.044; OR 6.17; 95% CI 1.05-35.71 and Pc = 0.0001; OR 5.5; 95% CI 2.4-12.4). The G allele of A2350G (Pa = 0.21; OR 1.74; 95% CI 0.73-4.17 and Pc = 0.007; OR 2.1; 95% CI 1.2-3.5) and G allele of G8790A (Pa = 0.002; OR 4.26; 95% CI 1.7-10.65 and Pc = 0.0001; OR 4.7; 95% CI 2.4-9.2) were more frequent in ICU-admitted patients and positive control group. Also lung involvement due to COVID-19 infection was associated with age and the comorbidities such as diabetes. In conclusion, our findings support the association between the wild genotype (GG) of ACE2 and homozygote genotype (GG) of ACE1 and sensitivity to COVID-19 infection, but not its severity. However, confirmation of this hypothesis requires further studies with more participants.
新型冠状病毒肺炎（COVID-19）与肾素-血管紧张素系统（RAS）之间存在关联，血管紧张素转换酶 2（ACE2）是 RAS 中的关键酶，已被证实是 SARS-CoV-2 的受体。功能性 ACE1/ACE2 基因多态性可能导致 ACE/ACE2 比值失衡，从而产生 RAS 失衡，这与急性呼吸窘迫综合征（ARDS）中更高程度的肺损伤有关，可能导致 COVID-19 感染结局的恶化。在此，我们研究了 RAS 基因多态性 ACE1（A2350G）和 ACE2（G8790A）作为 COVID-19 感染易感性和严重程度的风险预测因子的作用。共纳入 129 例：无 COVID-19 感染史的阴性对照组（n=50）、有 COVID-19 感染史但未住院的阳性对照组（n=35）和住院 ICU 的重症 COVID-19 感染患者（n=44）。采用 PCR-RFLP 法对 ACE 的 rs4343 和 ACE2 的 rs2285666 进行基因分型。我们的结果表明，COVID-19 感染的易感性与年龄、A2350G 的 GG 基因型（Pa=0.01；OR 4.7；95%CI 1.4-15.1 和 Pc=0.040；OR 2.5；95%CI 1.05-6.3）和 G8790A 的 GG 基因型（Pa=0.044；OR 6.17；95%CI 1.05-35.71 和 Pc=0.0001；OR 5.5；95%CI 2.4-12.4）有关。A2350G 的 G 等位基因（Pa=0.21；OR 1.74；95%CI 0.73-4.17 和 Pc=0.007；OR 2.1；95%CI 1.2-3.5）和 G8790A 的 G 等位基因（Pa=0.002；OR 4.26；95%CI 1.7-10.65 和 Pc=0.0001；OR 4.7；95%CI 2.4-9.2）在 ICU 住院患者和阳性对照组中更为常见。此外，COVID-19 感染导致的肺部受累与年龄和糖尿病等合并症有关。总之，我们的研究结果支持 ACE2 的野生基因型（GG）和 ACE1 的纯合基因型（GG）与 COVID-19 感染的敏感性之间存在关联，但与感染的严重程度无关。然而，要证实这一假设，还需要更多参与者的进一步研究。
