Genome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa 272-8516, Japan.
Intelligence for Medical and Nutritional Research, Tokyo 145-0065, Japan.
Genes (Basel). 2021 Oct 1;12(10):1572. doi: 10.3390/genes12101572.
The renin-angiotensin-aldosterone system (RAAS) appears to play an important role in SARS-CoV-2 infection. Polymorphisms within the genes that control this enzymatic system are candidates for elucidating the pathogenesis of COVID-19, since COVID-19 is not only a pulmonary disease but also affects many organs and systems throughout the body in multiple ways. Most striking is the fact that ACE2, one of the major components of the RAAS, is a prerequisite for SARS-COV-2 infection. Recently, we and other groups reported an association between a polymorphism of the gene (a homolog of ) and the phenotypic expression of COVID-19, particularly in its severity. The ethnic difference in insertion (I)/deletion (D) polymorphism seems to explain the apparent difference in mortality between the West and East Asia. The purpose of this review was to further evaluate the evidence linking polymorphisms to COVID-19. We searched the Medline database (2019-2021) for reference citations of relevant articles and selected studies on the clinical outcome of COVID-19 related to I/D polymorphism. Although the numbers of patients are not large enough yet, most available evidence supports the notion that the DD genotype adversely influences COVID-19 symptoms. Surprisingly, small studies conducted in several countries yielded opposite results, suggesting that the II genotype is a risk factor. This contradictory result may be the case in certain geographic areas, especially in subgroups of patients. It may also be due to interactions with other genes or to yet unexplained biochemical mechanisms. According to our hypothesis, such candidates are genes that are functionally involved in the pathophysiology of COVID-19, can act in concert with the DD genotype, and that show differences in their frequency between the West and East Asia. For this, we conducted research focusing on Alu-related genes. The current study on the genotype will provide potentially new clues to the pathogenesis, treatment, and diagnosis of SARS-CoV-2 infections.
肾素-血管紧张素-醛固酮系统（RAAS）似乎在 SARS-CoV-2 感染中发挥着重要作用。控制该酶系统的基因内的多态性是阐明 COVID-19 发病机制的候选者，因为 COVID-19 不仅是一种肺部疾病，而且还以多种方式影响全身许多器官和系统。最引人注目的是 ACE2，RAAS 的主要成分之一，是 SARS-COV-2 感染的先决条件。最近，我们和其他小组报告了基因（的同源物）的一个多态性与 COVID-19 的表型表达之间的关联，特别是在其严重程度方面。插入（I）/缺失（D）多态性的种族差异似乎可以解释西方和东亚之间死亡率的明显差异。本综述的目的是进一步评估将基因多态性与 COVID-19 联系起来的证据。我们在 Medline 数据库（2019-2021 年）中搜索了与相关文章的参考文献，并选择了与 COVID-19 相关的基因 I/D 多态性的临床结果的研究。尽管患者数量还不够大，但大多数现有证据支持这样一种观点，即 DD 基因型对 COVID-19 症状有不利影响。令人惊讶的是，在几个国家进行的小型研究得出了相反的结果，表明 II 基因型是一个危险因素。这种矛盾的结果可能在某些地理区域，特别是在某些患者亚组中出现。这也可能是由于与其他基因的相互作用或尚未解释的生化机制所致。根据我们的假设，这些候选者是在 COVID-19 病理生理学中具有功能作用的基因，可以与 DD 基因型协同作用，并且在西方和东亚之间的频率存在差异。为此，我们进行了专注于 Alu 相关基因的研究。目前对基因的研究将为 SARS-CoV-2 感染的发病机制、治疗和诊断提供潜在的新线索。
