Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran.
Mazandaran University of Medical Sciences, Farah-Abad Road, Sari, Mazandaran, Iran.
Mol Genet Genomics. 2023 Jan;298(1):27-36. doi: 10.1007/s00438-022-01953-8. Epub 2022 Oct 18.
Due to the unique affinity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the angiotensin-converting enzyme 2 (ACE2) receptor in patients, the foremost recent evidence indicated that ACE1 and ACE2 polymorphisms could affect the susceptibility of individuals to SARS-CoV-2 infection and also the disease outcome. Here, we aimed to assess the possible association between two polymorphisms and the severity of disease in patients. In the present study, 146 patients with COVID-19 who were admitted to the Mazandaran University of Medical Sciences hospitals between March 2020 and July 2020 were enrolled in this case-control study. The patients were divided into four groups based on clinical symptoms and severity of the diseases (mild, moderate, severe, and critical). After DNA extraction, the ACE gene I/D polymorphism (rs4646994) and ACE2 gene polymorphism (rs2285666) were genotyped using Gap-PCR and PCR-RFLP techniques, respectively. Then, five samples from each obtained genotype were confirmed by Sanger sequencing technique. Data were analyzed with SAS software version 9.1 using appropriate statistical procedures. The ACE gene I/D polymorphism (rs4646994) genotypes were classified into three types: I/I, I/D, and D/D. Our finding indicated that the prevalence of ACE1 D/D genotype was significantly higher in severe and critical COVID-19 patients (P = 0.0016). Additionally, the analysis revealed a remarkable association between rs4646994 SNP and the HB and ESRI levels in patients (P < 0.05). Although the ACE2 rs2285666 SNP was not related to the severity of disease, this variant was significantly associated with ALT, ESRI, and P. These results provide preliminary evidence of a genetic association between the ACE-D/D genotype and the D allele of ACE1 genotype and the disease severity. Therefore, our findings might be useful for identifying the susceptible population groups for COVID-19 therapy.
由于严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）与患者血管紧张素转换酶 2（ACE2）受体的独特亲和力，最近的主要证据表明，ACE1 和 ACE2 多态性可能影响个体对 SARS-CoV-2 感染的易感性和疾病结局。在这里，我们旨在评估两种多态性与患者疾病严重程度之间的可能关联。在本研究中，我们招募了 146 名 2020 年 3 月至 2020 年 7 月期间入住马赞达兰大学医学科学医院的 COVID-19 患者进行病例对照研究。根据临床症状和疾病严重程度（轻症、中度、重度和危重症）将患者分为四组。在提取 DNA 后，分别使用 Gap-PCR 和 PCR-RFLP 技术对 ACE 基因 I/D 多态性（rs4646994）和 ACE2 基因多态性（rs2285666）进行基因分型。然后，通过 Sanger 测序技术对每种获得的基因型的 5 个样本进行验证。使用适当的统计程序对数据进行分析。SAS 软件版本 9.1 用于分析数据。ACE 基因 I/D 多态性（rs4646994）基因型分为三种类型：I/I、I/D 和 D/D。我们的发现表明，严重和危重症 COVID-19 患者中 ACE1 D/D 基因型的患病率明显更高（P=0.0016）。此外，分析表明 rs4646994 SNP 与患者 HB 和 ESRI 水平之间存在显著关联（P<0.05）。虽然 ACE2 rs2285666 SNP 与疾病严重程度无关，但该变体与 ALT、ESRI 和 P 显著相关。这些结果提供了 ACE-D/D 基因型和 ACE1 基因型 D 等位基因与疾病严重程度之间遗传关联的初步证据。因此，我们的发现可能有助于确定 COVID-19 治疗的易感人群。
