Department of Medical Biochemistry and Molecular Biology, Mansoura University Faculty of Medicine, Mansoura, Egypt.
Department of Basic Medical Sciences, Faculty of Medicine, New Mansoura University, Mansoura, Egypt.
Virol J. 2024 Jan 23;21(1):27. doi: 10.1186/s12985-024-02298-x.
Since the emergence of the COVID-19 infection in China, it has caused considerable morbidity, mortality, and economic burden. It causes the vast majority of clinical manifestations, ranging from mild or even no symptoms to severe respiratory failure. There are many risk factors for severe COVID-19, such as old age, male gender, and associated comorbidities. A major role for genetic factors may exist. The SARS-CoV-2 virus enters the cell primarily through ACE2 receptors. rs2285666 is one of many polymorphisms found in the ACE2 receptor gene. To enable endosome-independent entry into target cells, the transmembrane protease serine-type 2 (TMPRSS2) is necessary to cleave the virus' spike (S) glycoprotein. TMPRSS2 is characterized by an androgen receptor element. The rs12329760 polymorphism in TMPRSS2 may explain different genetic susceptibilities to COVID-19.
This cross-sectional study was held in Mansoura University Hospitals during the period from June 2020 to April 2022 on patients who had mild and severe COVID-19. Demographic, clinical, and laboratory data were collected, and the TaqMan real-time polymerase chain was used for allelic discrimination in the genotyping of rs2285666 and rs12329760.
This study included 317 Egyptian patients, aged from 0.2 to 87 years. Males were 146, while females were 171. They were divided into mild and severe groups (91 and 226 patients, respectively) based on their clinical symptoms. There was a significant association between COVID-19 severity and male gender, hypertension, diabetes mellitus, and high CRP. The genotype and allele frequency distributions of the ACE2 rs2285666 polymorphism showed no significant association with the severity of COVID-19 in both. In contrast, in TMPRSS2 rs12329760 minor T allele and CT, TT genotypes were significantly associated with a reduced likelihood of developing severe COVID-19.
Our study indicates that the ACE2 rs2285666 polymorphism is not related to the severity of COVID-19, whether genotypes or alleles. In TMPRSS2 rs12329760, the dominant model and T allele showed significantly lower frequencies in severe cases, with a protective effect against severity. The discrepancies with previous results may be due to variations in other ACE2 receptor-related genes, inflammatory mediators, and coagulation indicators. Haplotype blocks and differences in racial makeup must be taken into consideration. Future research should be done to clarify how ethnicity affects these polymorphisms and how other comorbidities combine to have an additive effect.
自中国 COVID-19 感染出现以来，它已造成相当大的发病率、死亡率和经济负担。它导致了绝大多数临床表现，从轻症甚至无症状到严重呼吸衰竭不等。严重 COVID-19 有许多危险因素，如年龄较大、男性和相关合并症。遗传因素可能起着重要作用。SARS-CoV-2 病毒主要通过 ACE2 受体进入细胞。rs2285666 是 ACE2 受体基因中发现的许多多态性之一。为了使内体非依赖性进入靶细胞，跨膜丝氨酸蛋白酶 2（TMPRSS2）需要切割病毒的刺突（S）糖蛋白。TMPRSS2 的特征是雄激素受体元件。TMPRSS2 中的 rs12329760 多态性可能解释了 COVID-19 的不同遗传易感性。
这项横断面研究于 2020 年 6 月至 2022 年 4 月在曼苏拉大学医院对患有轻度和重度 COVID-19 的患者进行。收集了人口统计学、临床和实验室数据，并使用 TaqMan 实时聚合酶链反应对 rs2285666 和 rs12329760 的基因分型进行等位基因鉴别。
这项研究包括 317 名埃及患者，年龄从 0.2 岁到 87 岁。男性 146 人，女性 171 人。根据他们的临床症状，他们被分为轻度和重度组（分别为 91 例和 226 例患者）。COVID-19 严重程度与男性、高血压、糖尿病和高 C 反应蛋白显著相关。ACE2 rs2285666 多态性的基因型和等位基因频率分布与两者的 COVID-19 严重程度均无显著关联。相反，在 TMPRSS2 rs12329760 中，次要 T 等位基因和 CT、TT 基因型与发生严重 COVID-19 的可能性降低显著相关。
我们的研究表明，ACE2 rs2285666 多态性与 COVID-19 的严重程度无关，无论是基因型还是等位基因。在 TMPRSS2 rs12329760 中，显性模型和 T 等位基因在严重病例中的频率显著降低，对严重程度有保护作用。与之前的结果存在差异可能是由于 ACE2 受体相关基因、炎症介质和凝血指标的变化。必须考虑单倍型块和种族差异。未来的研究应该阐明种族如何影响这些多态性，以及其他合并症如何结合产生累加效应。
