PDF(Pubmed)
Abstract：
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.
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.
摘要：
背景：自中国出现COVID-19感染以来，它引起了相当大的发病率，死亡率,和经济负担。它引起了绝大多数的临床表现，从轻度甚至无症状到严重的呼吸衰竭。严重COVID-19有许多危险因素，如高龄，男性,和相关的合并症。可能存在遗传因素的主要作用。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。为了使不依赖内体的进入靶细胞，跨膜蛋白酶丝氨酸2型(TMPRSS2)是裂解病毒刺突(S)糖蛋白所必需的。TMPRSS2的特征在于雄激素受体元件。TMPRSS2中的rs12329760多态性可能解释了与COVID-19的不同遗传易感性。
方法：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进行，研究对象是轻度和重度COVID-19患者。人口统计,临床,收集了实验室数据，TaqMan实时聚合酶链用于rs2285666和rs12329760的基因分型中的等位基因区分。
结果：这项研究包括317名埃及患者，年龄在0.2至87岁之间。男性为146，女性为171。他们分为轻度和重度组（91例和226例患者，分别)根据他们的临床症状。COVID-19严重程度与男性之间存在显着关联，高血压,糖尿病,高CRP。ACE2rs2285666多态性的基因型和等位基因频率分布均与COVID-19的严重程度无明显相关性。相比之下,在TMPRSS2rs12329760次要T等位基因和CT中，TT基因型与发展为严重COVID-19的可能性降低显着相关。
结论：我们的研究表明，ACE2rs2285666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TMPRSS2rs12329760中，显性模型和T等位基因在重症病例中显示出明显较低的频率，对严重程度有保护作用。与先前结果的差异可能是由于其他ACE2受体相关基因的变化，炎症介质，和凝血指标。必须考虑单倍型障碍和种族构成的差异。未来的研究应该进行，以阐明种族如何影响这些多态性，以及其他合并症如何结合起来产生累加效应。
方法：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进行，研究对象是轻度和重度COVID-19患者。人口统计,临床,收集了实验室数据，TaqMan实时聚合酶链用于rs2285666和rs12329760的基因分型中的等位基因区分。
结果：这项研究包括317名埃及患者，年龄在0.2至87岁之间。男性为146，女性为171。他们分为轻度和重度组（91例和226例患者，分别)根据他们的临床症状。COVID-19严重程度与男性之间存在显着关联，高血压,糖尿病,高CRP。ACE2rs2285666多态性的基因型和等位基因频率分布均与COVID-19的严重程度无明显相关性。相比之下,在TMPRSS2rs12329760次要T等位基因和CT中，TT基因型与发展为严重COVID-19的可能性降低显着相关。
结论：我们的研究表明，ACE2rs2285666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TMPRSS2rs12329760中，显性模型和T等位基因在重症病例中显示出明显较低的频率，对严重程度有保护作用。与先前结果的差异可能是由于其他ACE2受体相关基因的变化，炎症介质，和凝血指标。必须考虑单倍型障碍和种族构成的差异。未来的研究应该进行，以阐明种族如何影响这些多态性，以及其他合并症如何结合起来产生累加效应。
