The DOI matches its Crossref record; 56 of the 66 references it cites were found in a registry or an index.
SARS-CoV-2 infections and COVID-19 mortalities strongly correlate with ACE1 I/D genotype
Open accessAbstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). The relentless spread and pathogenicity of the virus have become a global public health emergency. One of the striking features of this pandemic is the pronounced impact on specific regions and ethnic groups. In particular, compared with East Asia, where the virus first emerged, SARS-CoV-2 has caused high rates of morbidity and mortality in Europe. This has not been experienced in past global viral infections, such as influenza, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and is unique to SARS-CoV-2. For this reason, we investigated the involvement of genetic factors associated with SARS-CoV-2 infection with a focus on angiotensin-converting enzyme (ACE)-related genes, because ACE2 is a receptor for SARS-CoV-2. We found that the ACE1 II genotype frequency in a population was significantly negatively correlated with the number of SARS-CoV-2 cases. Similarly, the ACE1 II genotype was negatively correlated with the number of deaths due to SARS-CoV-2 infection. These data suggest that the ACE1 II genotype may influence the prevalence and clinical outcome of COVID-19 and serve as a predictive marker for COVID-19 risk and severity.
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“Furthermore, the ACE1 II genotype is protective against COVID-19 as compared to the ACE1 DD genotype (358), and serum levels of ACE1 are higher in the DD genotype compared with the II genotype (359).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [358]
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Cites
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“Moreover, because ACE2 is a receptor for SARS-COV-2 (Hoffmann et al., 2020), viral infection may lead to the suppression of ACE2 function and cause ACE1/ACE2 imbalance responsible for RAAS over-activation and pulmonary shutdown (Gemmati et al., 2020).”
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“Therefore, the balance between ACE1 and ACE2 is considered to be very important for maintaining homeostasis in the body (Chappel and Ferrario, 2006; Gemmati et al., 2020).”
BackgroundVariation in DCP1, encoding ACE, is associated with susceptibility to Alzheimer disease
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“Under physiological conditions, the signal from angiotensin (Ang) II generated by ACE1 is related to pathological conditions such as vasoconstriction, inflammation and fibrosis, and ACE2-derived peptide, Ang 1–7, reverses the action of Ang II via the Mas receptor (Xiao et al., 2020).”
Background
Research works printed but not linked: 4
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Cited by
Sorted by citations
Items 101–125 of 125
Bragina, A., Tarzimanova, A., Rodionova, Y., Ogibenina, E. S., Suvorov, A., Druzhinina, N., Vasilyeva, L., Ishina, T. I., Medvedev, I., Borlakova, M., et al. (2024) · Journal of Clinical Medicine Research · doi:10.14740/jocmr5223 · Cited by 2
“The results of a study by Yamamoto et al about the negative correlation of the ACE1 I/I genotype with susceptibility to SARS-CoV-2 infection confirm this [29].”
ResultSamet, M., Yazdi, M., Tajamolian, M., Beygi, M., Sheikhha, M., & Hoseini, S. M. (2023) · Biochemical Genetics · doi:10.1007/s10528-023-10614-3 · Cited by 2
“…allele (D-dominant model) (Mir, et al. 2021; Çobanogul-lari 2023), while others have suggested its positive effect to decrease infection and mortality rates due to the presence of protective I allele (I-dominant model) (Soltani Rezaiezadeh et al. 2022; Yamamoto et al. 2020; Calabrese et al. 2020).”
Abbaszadeh, H., Mohammadi, F., Rajabi-Moghaddam, M., Kabiri-rad, H., Ghafari, S., Abedi, F., & Miri-Moghaddam, E. (2022) · Clinica chimica acta; international journal of clinical chemistry · doi:10.1016/j.cca.2022.09.006 · Cited by 2
Kocak, F., Akcılar, R., Kar, F., Isiklar, O., Atlanoğlu, Ş., Genç, Ö., & Yaman, F. (2022) · Turkish Journal of Biochemistry · doi:10.1515/tjb-2021-0281 · Cited by 2
Ichiyanagi, K., & Saito, K. (2022) · Mobile DNA · doi:10.1186/s13100-022-00261-7 · Cited by 2
“Interestingly, there was a significant negative correlation between the frequency of the inserted allele in a population and the number of SARS-CoV-2 cases and the number of deaths due to SARS-CoV-2 infection [17].”
BackgroundThe Association Between ACE I/D and ACE2 rs2285666 Polymorphisms with COVID-19 Disease Severity
Drikvand, S., Ajorloo, M., Birjandi, M., & Shahsavari, G. (2025) · Genetic Testing and Molecular Biomarkers · doi:10.1177/19450265251396705 · Cited by 1
“Yamamoto et al. propose an inverse association between genotype II and the prevalence and (Yamamoto et al., 2020).”
Bragina, A., Rodionova, Y., Ogibenina, E. S., Fomin, A. S., & Podzolkov, V. (2024) · Терапевтический архив · doi:10.26442/00403660.2024.09.202849 · Cited by 1
Homozygous-Recessive Characteristics as a Biomarker of Predisposition for COVID-19
Grujičić, D., Mirkov, L., Banković, D., Virijević, K., Marinkoviĉ, D., & Milošević-Djordjević, O. (2023) · Clinical Nursing Research · doi:10.1177/10547738221147754 · Cited by 1
Íñiguez, M., Pérez-Matute, P., Villoslada-Blanco, P., Recio-Fernández, E., Ezquerro-Pérez, D., Alba, J., Ferreira-Laso, M., & Oteo, J. (2021) · medRxiv · doi:10.1101/2021.03.24.21253576 · Cited by 1
“In fact, several studies have suggested that variabilities in the genotype distribution of ACE polymorphisms could explain the variable prevalence and clinical outcomes of COVID-19 among different regions of the world (20-22).”
BackgroundRole of Ecologic ACE I/D Polymorphism Data Towards Prediction of COVID-19 Epidemiology
Amar, A., Khan, A. R., Shakoor, M., Abid, A., & Khaliq, S. (2021) · doi:10.21203/rs.3.rs-259633/v1 · Cited by 1
“Previously various studies reported association of ACE I/D polymorphism either with COVID-19 prevalence [13-16], or mortality (affected by COVID-19 testing intensity) or deaths/million (independent of COVID-19 testing intensity) [15,16,11,17] or with recovery rate [18].”
BackgroundACE Polymorphism and Clinical Outcomes in Iranian Patients with COVID-19
Soltani, S., Tabibzadeh, A., Yousefi, P., Farahani, A., Didehdar, M., Abedi, B., & Khodashenas, S. (2026) · Jundishapur Journal of Microbiology · doi:10.5812/jjm-172133
Çobanoğulları, H., Koyutourk, B., Daoud, M. A., Fahrioğlu, U., Sayan, M., & Ergoren, M. C. (2026) · Human Gene · doi:10.1016/j.humgen.2026.201556
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“Regional differences in allele frequencies may explain variations in COVID-19 incidence and mortality rates, as suggested by Yamamoto et al. 36 Figure 1 depicts the sequential pathway of heart failure development, emphasizing the role of ACE and angiotensin II, associated symptoms, diagnostic markers, therapeutic inte…”
Ibadullaeva, N., Musabaev, E., Khikmatullaeva, A., & Padyukov, L. (2026) · BMC Infectious Diseases · doi:10.1186/s12879-026-12798-6
“On the other hand, the European population has a higher frequency of the ACE DD genotype [32] and a higher prevalence and mortality from COVID-19 than the Asian population does [33].”
Bouchikhi, I. E., Otmani, I. E., Ahakoud, M., Kettani, O., Elmakhzen, B., Yahyaoui, G., Oumokhtar, B., Ouldim, K., El-Azami-El-Idrissi, M., Achour, S., et al. (2025) · Molecular Biology Reports · doi:10.1007/s11033-024-10211-6
Shahrebabaki, A. M., Nikseresht, M., Mahmoodi, M., Zarei, S., Hosseiniara, R., Esmaeili, O. S., Mirzaei, M. R., Kahnooji, M., & Hajizadeh, M. (2024) · Viral immunology · doi:10.1089/vim.2024.0071
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“A strong correlation between mortality from COVID-19 in patients with the DD genotype and ACE ID gene has been reported by other researchers [18], who believe that this genotype may also be an informative prognostic marker of the new coronavirus disease severity.”
BackgroundAre COVID-19 Polymorphisms in ACE and ACE2 Prognosis Predictors?
Guarienti, F. A., Xavier, F., Ferraz, M. D., Wagner, F., Marinowic, D., da Costa, J. C., & Machado, D. C. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46080480
“Therefore, the deletion allele is associated with COVID-19 progression [14] and SARS-CoV-2 infection rate and mortality, while the ACE-I/I genotype negatively correlates with infection rate and mortality [15].”
BackgroundEstudio del valor de Ct y el polimorfismo D/I del gen ECA1 en la respuesta al SARS-COV-2
Quintana, S., Giustina, S., Belmonte, J. M., Gerónimo, V. M. D., Fedele, S., Sanz, Y., Ligorino, G., Goria, N., Giletto, G., Rivero, M., et al. (2023) · Revista Bioquímica y Patología Clínica · doi:10.62073/bypc.v87i1.239
HLA and Red Blood Cell Antigen Genotyping in SARS-CoV-2 Convalescent Plasma Donors
Lemieux, W., Perreault, J., Leiva‐Torres, G. A., Baillargeon, N., Constanzo‐Yanez, J., Chevrier, M., Richard, L., Lewin, A., & Trépanier, P. (2023) · Future Virology · doi:10.2217/fvl-2022-0058
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Trépanier, P., Perreault, J., Leiva, G., Baillargeon, N., Yanez, J., Chevrier, M.-C., & Lewin, A. (2021) · medRxiv · doi:10.1101/2021.03.17.21253821
Izzedine, H., Jhaveri, K., & Perazella, M. (2021) · Clinical Kidney Journal · doi:10.1093/ckj/sfab044
COVID-19 and Renin Angiotensin Aldosterone System: A Pharmacogenomic View.
Eldesoky, E. (2021) · American Journal of Therapeutics · doi:10.1097/mjt.0000000000001299
Yu.I., C., L.Ye., F., G., G. N., I, K., L., M., I., P. V., I., R. Z., M., T., & O., V. V. (2020) · Ukrainian Medical Journal · doi:10.32471/umj.1680-3051.196058
Metadata
- Authors
- Yamamoto, N., Ariumi, Y., Nishida, N., Yamamoto, R., Bauer, G., Gojobori, T., Shimotohno, K., & Mizokami, M.
- Affiliations
- National Center for Global Health and Medicine (JP)
- Joint Research Center for Human Retrovirus Infection, Kumamoto University (JP)
- Keio University (JP)
- University of Freiburg (DE)
- King Abdullah University of Science and Technology (SA)
- Corresponding author
- Yamamoto, Naoki
- Shimotohno, Kunitada
- Mizokami, Masashi
- ORCID
- Venue
- Gene
- Publisher
- Elsevier BV
- Published
- 2020-10
- Volume
- 758
- Pages
- 144944
- ISSN
- 0378-1119 (ISSN-L)
- PMC
- PMC7833925
- OpenAlex
- W3038462367
- Cited by
- 141
- References
- 66
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 15 · 2023: 20 · 2022: 36 · 2021: 54 · 2020: 11
- FWCI
- 3.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gene (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- King Abdullah University of Science and Technology Repository (King Abdullah University of Science and Technology) (submittedVersion, cc-by-nc-nd)
- Funders
- Japan Society for the Promotion of Science (18K08438)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- SARS-CoV-2, COVID-19 pandemic, ACE2 receptor, genetic susceptibility, COVID-19 mortality
- MeSH terms
- Betacoronavirus, Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Asia, Europe, Gene Frequency, Genotype, Humans, Peptidyl-Dipeptidase A, Pneumonia, Viral, Risk, Risk Factors, Severity of Illness Index, Treatment Outcome, Coronavirus Infections, Polymorphism, Single Nucleotide, Pandemics
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