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Review

Angiotensin–Converting Enzyme (ACE) 1 Gene Polymorphism and Phenotypic Expression of COVID-19 Symptoms

1
Genome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa 272-8516, Japan
2
Intelligence for Medical and Nutritional Research, Tokyo 145-0065, Japan
3
Computational Bioscience Research Center, Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia
4
Division of Retroelement, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 860-0811, Japan
*
Author to whom correspondence should be addressed.
Academic Editors: Michele Cioffi and Maria Teresa Vietri
Genes 2021, 12(10), 1572; https://doi.org/10.3390/genes12101572
Received: 6 August 2021 / Revised: 16 September 2021 / Accepted: 28 September 2021 / Published: 1 October 2021
(This article belongs to the Collection Genotype-Phenotype Study in Disease)
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 ACE1 gene (a homolog of ACE2) and the phenotypic expression of COVID-19, particularly in its severity. The ethnic difference in ACE1 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 ACE1 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 ACE1 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 ACE1 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 ACE1 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 ACE1 genotype will provide potentially new clues to the pathogenesis, treatment, and diagnosis of SARS-CoV-2 infections. View Full-Text
Keywords: SARS-CoV-2; COVID-19 symptoms; ACE1 I/D polymorphism; Alu; RAAS; comorbidities SARS-CoV-2; COVID-19 symptoms; ACE1 I/D polymorphism; Alu; RAAS; comorbidities
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MDPI and ACS Style

Yamamoto, N.; Nishida, N.; Yamamoto, R.; Gojobori, T.; Shimotohno, K.; Mizokami, M.; Ariumi, Y. Angiotensin–Converting Enzyme (ACE) 1 Gene Polymorphism and Phenotypic Expression of COVID-19 Symptoms. Genes 2021, 12, 1572. https://doi.org/10.3390/genes12101572

AMA Style

Yamamoto N, Nishida N, Yamamoto R, Gojobori T, Shimotohno K, Mizokami M, Ariumi Y. Angiotensin–Converting Enzyme (ACE) 1 Gene Polymorphism and Phenotypic Expression of COVID-19 Symptoms. Genes. 2021; 12(10):1572. https://doi.org/10.3390/genes12101572

Chicago/Turabian Style

Yamamoto, Naoki, Nao Nishida, Rain Yamamoto, Takashi Gojobori, Kunitada Shimotohno, Masashi Mizokami, and Yasuo Ariumi. 2021. "Angiotensin–Converting Enzyme (ACE) 1 Gene Polymorphism and Phenotypic Expression of COVID-19 Symptoms" Genes 12, no. 10: 1572. https://doi.org/10.3390/genes12101572

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