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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The ACE1 II genotype is protective against COVID-19 as compared to the ACE1 DD genotype.
“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]
The Results report that countries with higher ACE1 II genotype frequencies had fewer SARS-CoV-2 cases and COVID-19 deaths, and the Discussion predicts greater disease severity in DD carriers. These population-level correlations and predictions are consistent with a protective effect, but the paper does not establish that individuals with the II genotype are protected relative to individuals with the DD genotype; the Conclusions call for clinical outcomes in those carriers to be assessed. (LLM, conf=0.87)
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“In terms of RAAS‐related genes, intron 16 of human ACE1 gene on chromosome 17 contains an Alu repeat insertion (I) or deletion (D).10 According to its variations, there are three distinctive genotypes: II, ID, and DD.11 A common I/D variant in ACE gene has been previously linked with several pathological conditions.12…”
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“recently reported detailed information on ACE1 I/I genotype rates among European, Middle Eastern, South Asian and East Asian countries, merging data from the Center for Systems Science and Engineering at Johns Hopkins University detailing ACE1 I/I genotype frequencies, number of affected cases/population and number of…”
BackgroundResultInfluentialGenetic and epigenetic factors associated with increased severity of Covid‐19
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“Many studies described the association of the RAS component genetic variation with the prevalence of COVID-19 diseases [47,68].”
BackgroundInfluentialCafiero, C., Rosapepe, F., Palmirotta, R., Re, A., Ottaiano, M., Benincasa, G., Perone, R., Varriale, E., D’Amato, G., Cacciamani, A., et al. (2021) · Pharmacogenomics and Personalized Medicine · doi:10.2147/pgpm.s303666 · Cited by 53
“The results of this study, albeit with a limited but wellselected number of patients, suggest that some gene variants of RAAS pathway could modulate some pathological conditions associated with the heterogeneous clinical picture caused by SARS-CoV-2 infection such as disseminated intravascular coagulation and thrombos…”
ResultPrecision Medicine and Public Health: New Challenges for Effective and Sustainable Health
Traversi, D., Pulliero, A., Izzotti, A., Franchitti, E., Iacoviello, L., Gianfagna, F., Gialluisi, A., Izzi, B., Agodi, A., Barchitta, M., et al. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11020135 · Cited by 73 · see citing works
“Another study investigated the involvement of genetic factors associated with SARS-CoV-2 infection, particularly ACE-related genes [164], showing a negative correlation with the number of cases and number of deaths due to viral infection, since both decreased with an increasing”
BackgroundDieter, C., Brondani, L. D. A., Leitão, C., Gerchman, F., Lemos, N. E., & Crispim, D. (2022) · PLoS ONE · doi:10.1371/journal.pone.0270627 · Cited by 48 · see citing works
“This Ins/Del variant results in alternative splicing, leading to protein shortening and loss of the catalytically active domain in ACE1 Ins allele carriers [92].”
BackgroundHuman gene polymorphisms and their possible impact on the clinical outcome of SARS-CoV-2 infection
Hashemi, S. M. A., Thijssen, M., Hosseini, S. Y., Tabarraei, A., Pourkarim, M. R., & Sarvari, J. (2021) · Archives of Virology · doi:10.1007/s00705-021-05070-6 · Cited by 53 · see citing works
Öz, M., & Lorke, D. E. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.111193 · Cited by 55 · see citing works
Balzanelli, M., Distratis, P., Lazzaro, R., Phạm, V., Tran, T. C., Dipalma, G., Bianco, A., Serlenga, E., Aityan, S., Pierangeli, V., et al. (2022) · Diagnostics · doi:10.3390/diagnostics12112824 · Cited by 46 · see citing works
Ishak, A., Mehendale, M., AlRawashdeh, M. M., Sestacovschi, C., Sharath, M., Pandav, K., & Marzban, S. (2022) · Gene · doi:10.1016/j.gene.2022.146674 · Cited by 44 · see citing works
Potential Genes Associated with COVID-19 and Comorbidity
Feng, S., Song, F.-Q., Guo, W., Tan, J.-S., Zhang, X.-Q., Qiao, F., Guo, J.-L., Zhang, L., & Jia, X. (2022) · International Journal of Medical Sciences · doi:10.7150/ijms.67815 · Cited by 41 · see citing works
“The frequency and mortality of COVID-19 patients are closely connected to the ACE-I/D genotype that may be detected for predicting the ponderance of COVID-19 [70].”
BackgroundCalabrese, C., Annunziata, A., Coppola, A., Pafundi, P., Guarino, S., Spirito, V. D., Maddaloni, V., Pepe, N., & Fiorentino, G. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2020.631148 · Cited by 41 · see citing works
Mir, R., Mir, R., Alghamdi, M. A. A., Alsayed, B. A., Wani, J. I., Alharthi, M. H., & Alshahrani, A. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11111098 · Cited by 43 · see citing works
“Role of RAAS in SARS-CoV-2 Infection Different ACE genotypes are believed to be associated with development of acute respiratory distress syndrome and several studies have reported that the distribution frequency of ACE insertion/insertion (II) genotype might have a significant influence on COVID-19 mortality [36,40].”
BackgroundAdli, A., Rahimi, M., Khodaie, R., Hashemzaei, N., & Hosseini, S. M. (2022) · Journal of Medical Virology · doi:10.1002/jmv.27615 · Cited by 43 · see citing works
ACE I/D polymorphism in Czech first-wave SARS-CoV-2-positive survivors
Hubáček, J., Dušek, L., Májek, O., Adámek, V., Červinková, T., Dlouhá, D., & Adámková, V. (2021) · Clinica chimica acta; international journal of clinical chemistry · doi:10.1016/j.cca.2021.04.024 · Cited by 39
“Studies performed on Asian populations [24,28,29], reported opposite results and suggested a D/D genotype as a predictive marker of COVID-19 severity.”
Kouhpayeh, H., Tabasi, F., Dehvari, M., Naderi, M., Bahari, G., Khalili, T., Clark, C., Ghavami, S., & Taheri, M. (2021) · Translational Medicine Communications · doi:10.1186/s41231-021-00106-0 · Cited by 38 · see citing works
“also showed that the II genotype has a strong negative correlation with COVID-19 prevalence and death [59].”
BackgroundCCR5Delta32 deletion as a protective factor in Czech first-wave COVID-19 subjects.
Hubacek, J., Dušek, L., Májek, O., Adámek, V., Červinková, T., Dlouhá, D., Pavel, J., & Adámková, V. (2021) · Physiological Research · doi:10.33549/physiolres.934647 · Cited by 38
What could explain the late emergence of COVID-19 in Africa?
Lalaoui, R., Bakour, S., Raoult, D., Verger, P., Sokhna, C., Devaux, C. A., Pradines, B., & Rolain, J. (2020) · New Microbes and New Infections · doi:10.1016/j.nmni.2020.100760 · Cited by 38 · see citing works
Proline Isomerization: From the Chemistry and Biology to Therapeutic Opportunities
Gurung, D., Danielson, J. A., Tasnim, A., Zhang, J.-T., Zou, Y., & Liu, J.-Y. (2023) · Biology · doi:10.3390/biology12071008 · Cited by 36 · see citing works
“Using cyclophilin inhibitors and RNA interference experiments, several groups have shown that CypA directly binds to HBX [212], and promotes HBV replication, production and secretion [213–215].”
BackgroundHuman genetic basis of coronavirus disease 2019
Deng, H., Yan, X., & Yuan, L.-M. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00736-8 · Cited by 35 · see citing works
“Middle Eastern populations, particularly those in Lebanon with a relatively low I-allele frequency, are believed to be the ancestor of the ACE variant.(86) I/I genotype increases westwards and eastwards from the Middle East.”
BackgroundMouliou, D. S., Kotsiou, O. S., & Gourgoulianis, K. I. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18168701 · Cited by 37 · see citing works
“COVID-19 prevalence has negatively been correlated with ACE1 I allele frequency [31].”
BackgroundMilani, D., Caruso, L., Zauli, E., Owaifeer, A. M. A., Secchiero, P., Zauli, G., Gemmati, D., & Tisato, V. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.871583 · Cited by 34 · see citing works
“The main activity of these enzymes is significantly driven by common intragenic polymorphisms also characterized by a peculiar geographic distribution that disclosed exciting correspondences between haplotypes distribution and worldwide COVID-19 morbidity and mortality index (Yamamoto et al., 2020).”
BackgroundTakeshita, M., Nishina, N., Moriyama, S., Takahashi, Y., Uwamino, Y., Nagata, M., Aoki, W., Masaki, K., Ishii, M., Saya, H., et al. (2021) · Virology · doi:10.1016/j.virol.2020.12.020 · Cited by 31 · see citing works
“Several hypotheses, such as the difference in genetic backgrounds, socio-behavioral differences, mutations in SARS-CoV-2 genomes, and the possibility of having cross-reactive immunity to similar viruses, are inferred as causes of this difference but has not been identified (Yamamoto et al., 2020; Ng et al., 2020; Fors…”
Yamamoto, N., Nishida, N., Yamamoto, R., Gojobori, T., Shimotohno, K., Mizokami, M., & Ariumi, Y. (2021) · Genes · doi:10.3390/genes12101572 · Cited by 29 · see citing works
“Conversely, the number of cases and deaths in other regions, especially in largely populated East Asia, is much lower, and the racial differences are noteworthy [5].”
BackgroundSelf-citationBeauty and the beast: host microRNA-155 versus SARS-CoV-2
Papadopoulos, K., Papadopoulou, A., & Aw, T. (2023) · Human Cell · doi:10.1007/s13577-023-00867-w · Cited by 27 · see citing works
COVID-19 and syndemic challenges in ‘Battling the Big Three’: HIV, TB and malaria
Velavan, T., Meyer, C., Esen, M., Kremsner, P., & Ntoumi, F. (2021) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2021.03.071 · Cited by 27
Castelo-Branco, L., Tsourti, Z., Gennatas, S., Rogado, J., Sekacheva, M., Viñal, D., Lee, R., Croitoru, A., Vitorino, M., Khallaf, S., et al. (2022) · ESMO Open · doi:10.1016/j.esmoop.2022.100499 · Cited by 26 · see citing works
“Notably, a strong correlation was found between ACE1 II genotype, more frequent in Asians, and lower severity or death from COVID19.(39) All these factors may justify the favourable survival”
Yamamoto, N., Yamamoto, R., Ariumi, Y., Mizokami, M., Shimotohno, K., & Yoshikura, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22095000 · Cited by 26 · see citing works
“We recently reported significantly different infection and mortality rates for SARS-CoV-2 between European and East Asian populations, and this correlated with the ACE1 D/I genotype [7,8].”
Self-citationPabalan, N., Tharabenjasin, P., Suntornsaratoon, P., Jarjanazi, H., & Muanprasat, C. (2020) · Infection Genetics and Evolution · doi:10.1016/j.meegid.2020.104682 · Cited by 26 · see citing works
“The strong negative correlation between ACE II genotype frequency and the number of cases, as well as deaths from COVID-19 suggests a role for ACE II in the clinical outcome of COVID-19 and may be a predictive marker for COVID-19 risk (Yamamoto et al., 2020).”
Suh, S., Lee, S., Gym, H., Yoon, S., Park, S.-K., Cha, J., Kwon, D., Yang, Y.-S., & Sun, H.-J. (2022) · BMC Infectious Diseases · doi:10.1186/s12879-022-07034-w · Cited by 22
Íñiguez, M., Pérez-Matute, P., Villoslada-Blanco, P., Recio-Fernández, E., Ezquerro-Pérez, D., Alba, J., Ferreira-Laso, M., & Oteo, J. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.688071 · Cited by 22
Cumpstey, A. F., Clark, A. D., Santolini, J., Jackson, A. A., & Feelisch, M. (2021) · Antioxidants and Redox Signaling · doi:10.1089/ars.2021.0017 · Cited by 40 · see citing works
“The higher population frequency of this ACE insertion polymorphism also correlates strongly with both lower SARS-CoV-2 infection and COVID-19 mortality rate (467).”
Al-Eitan, L., & Alahmad, S. (2020) · Reviews in Medical Virology · doi:10.1002/rmv.2194 · Cited by 22 · see citing works
“to correlate with the variations in outcomes where populations with a high D genotype frequency tend to experience higher mortality rates.(39,40) Another study indicates that I/D polymorphism in the ACE1 gene is linked to the severity of the SARS‐CoV‐2 infection depending on the hypertensive condition of the patient.”
ResultSaad, H., Jabotian, K., Sakr, C. J., Mahfouz, R., Akl, I. B., & Zgheib, N. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.798571 · Cited by 21
Triple jeopardy in ageing: COVID-19, co-morbidities and inflamm-ageing
Rea, I. M., & Alexander, H. D. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101494 · Cited by 27 · see citing works
Keikha, M., & Karbalaei, M. (2022) · Microbial Pathogenesis · doi:10.1016/j.micpath.2022.105781 · Cited by 18
“In this pathway, the angiotensinconverting enzyme (ACE or ACE1) converts angiotensin-1 (Ang-1) to Ang-2; on the other hand, ACE2 converts Ang-2 to Ang-(1-7) (6).”
InfluentialPapadopoulou, A., Fragkou, P., Maratou, E., Dimopoulou, D., Kominakis, A., Kokkinopoulou, I., Kroupis, C., Nikolaidou, A., Antonakos, G., Papaevangelou, V., et al. (2021) · Journal of Medical Virology · doi:10.1002/jmv.27417 · Cited by 18 · see citing works
“In the early pandemic, an extensive debate has been launched regarding the effect of the ACE I/D alleles on the prevalence and the outcome of the COVID‐19 infection.(7,8) First, Delanghe et al.”
BackgroundResultInfluentialA new framework for host-pathogen interaction research
Yu, H., Li, L., Huffman, A., Beverley, J., Hur, J., Merrell, E. C., Huang, H.-H., Wang, Y., Liu, Y.-T., Ong, E., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1066733 · Cited by 17 · see citing works
“For example, hosts exhibiting the angiotensin converting enzyme 1 (ACE-1) II genotype, which is more prevalent in Western Europe and steadily decreases in frequency towards Eastern Asia, appears to negatively correlate with the manifestation of COVID-19, and thus related mortality rates (34).”
BackgroundFaridzadeh, A., Mahmoudi, M., Ghaffarpour, S., Zamani, M., Hoseinzadeh, A., Naghizadeh, M., & Ghazanfari, T. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.955965 · Cited by 17 · see citing works
“The prevalence and mortality rates of COVID-19 vary considerably from country to country, which raises the question of whether geographical origin and host genetic variations play a role in the severity and mortality of COVID19 infection.”
BackgroundInfluentialGenetics of COVID‐19 and myalgic encephalomyelitis/chronic fatigue syndrome: a systematic review
Tziastoudi, M., Cholevas, C., Stefanidis, I., & Theoharides, T. (2022) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51631 · Cited by 16 · see citing works
Association investigations between ACE1 and ACE2 polymorphisms and severity of COVID-19 disease
Najafi, M., & Mahdavi, M. (2022) · Zeitschrift für Induktive Abstammungs- und Vererbungslehre · doi:10.1007/s00438-022-01953-8 · Cited by 15
“1 3 on Asian populations (Pourbagheri-Sigaroodi et al. 2020; Yamamoto et al. 2020; Verma et al. 2021), reflecting the ethnicity-specific allelic effect.”
BackgroundJevnikar, K., Lapajne, L., Petrovič, D., Meglič, A., Logar, M., Valentinčič, N. V., Globočnik-Petrovič, M., Cileňsek, I., & Mekjavić, P. (2022) · Genes · doi:10.3390/genes13071111 · Cited by 15 · see citing works
“Individuals with a D/D genotype were shown to have a higher incidence of pulmonary embolism and increased mortality rates, possibly due to increased levels of serum ACE [19,27,28].”
BackgroundRestoring Trust: The Need for Precision Medicine in Infectious Diseases, Public Health and Vaccines
Equils, O., Bakaj, A., Wilson-Mifsud, B., & Chatterjee, A. (2023) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2023.2234787 · Cited by 15 · see citing works
Malinowska, J. K., & Żuradzki, T. (2022) · Medicine Health Care and Philosophy · doi:10.1007/s11019-022-10122-y · Cited by 21 · see citing works
Human genetic basis of severe or critical illness in COVID-19
Ji, X., Chen, B., Ze, B., & Zhou, W.-H. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.963239 · Cited by 14 · see citing works
“Another study also revealed a strong correlation between ACE1 insertion/deletion (I/D) genotype with COVID-19 mortalities (Yamamoto et al., 2020).”
BackgroundRepurposing of approved drugs with potential to interact with SARS-CoV-2 receptor
Ahsan, T., & Sajib, A. (2020) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2021.100982 · Cited by 13 · see citing works
Rezaiezadeh, J. S., Lord, J. S., Yekaninejad, M., & Izadi, P. (2022) · Human Gene · doi:10.1016/j.humgen.2022.201099 · Cited by 12
“Comparison of ACE1 genotypes frequencies data in different ethnicities with reported COVID-19 cases and mortality rate, showed that the frequency of ACE1 II genotype was negatively correlated with the number of SARS-CoV-2 infected cases and number of deaths due to SARS-CoV-2 infection (28).”
ResultHubáček, J. (2021) · Physiological Research · doi:10.33549/physiolres.934730 · Cited by 12 · see citing works
Age and genotype dependent erythropoietin protection in COVID-19
Papadopoulos, K. I., Sutheesophon, W., Manipalviratn, S., & Aw, T. C. (2021) · World Journal of Stem Cells · doi:10.4252/wjsc.v13.i10.1513 · Cited by 13 · see citing works
Oscanoa, T., Vidal, X., Coto, E., & Romero-Ortuño, R. (2021) · Arterial Hypertension · doi:10.5603/ah.a2021.0018 · Cited by 12 · see citing works
Boraey, N. F., Bebars, M. A., Wahba, A. A., El-Lateef, H. M. A., Attia, M., Elsayed, A. H., Rashed, K., Sorour, E., Ahmed, M. F., Abd-Elrehim, G. A. B., et al. (2024) · Pediatric Research · doi:10.1038/s41390-023-02982-8 · Cited by 11 · see citing works
“27,28 Verma et al. reported that carrying the ACE1 D/D genotype was associated with a 3.6-fold higher risk of severe COVID-19 in Indian population.”
InfluentialHost polymorphisms and COVID-19 infection
Delanghe, J., & Speeckaert, M. (2021) · Advances in Clinical Chemistry · doi:10.1016/bs.acc.2021.07.002 · Cited by 11 · see citing works
“correlated with susceptibility to SARS-CoV-2 infection and consequent mortality [56].”
BackgroundExploring AyuGenomics approach for understanding COVID-19 predisposition and progression
Bhat, V., Borse, S. P., Chavan-Gautam, P., & Joshi, K. (2021) · Journal of Ayurveda and Integrative Medicine · doi:10.1016/j.jaim.2021.06.003 · Cited by 11 · see citing works
“n between ACE1 II genotype and COVID-19 cases and deaths [55]”
Kusi, K., Frimpong, A., Partey, F., Lamptey, H., Amoah, L., & Ofori, M. (2021) · AAS Open Research · doi:10.12688/aasopenres.13196.3 · Cited by 11 · see citing works
“Indeed, Southern Asia has also recorded very few SARS-CoV-2 related severe disease and deaths 49 .”
Elbasan, O., Bayram, F., Yazan, C. D., Apaydın, T., Dashdamirova, S., Polat, H., Arslan, E., Yilmaz, I., Karimi, N., Sengel, B. E., et al. (2023) · PLoS ONE · doi:10.1371/journal.pone.0288338 · Cited by 10
“Although many studies have shown an association of the ACE DD genotype with the severity of COVID-19, others have indicated conflicting results [15, 17, 18, 25].”
BackgroundResultFiorentino, G., Benincasa, G., Coppola, A., Franzese, M., Annunziata, A., Affinito, O., Viglietti, M., & Napoli, C. (2022) · Journal of Thrombosis and Thrombolysis · doi:10.1007/s11239-022-02728-z · Cited by 9 · see citing works
Genetics and Molecular Biology
Cumming, A. M. (2021) · doi:10.1097/00041433-199206000-00014 · Cited by 9
Sacuena, E. R. P., Lima, C. N. C., Abreu, I., da Silva, L. M. C., Belleza, L. K. G., Lemes, R. B., de Araújo, G. S., da Silva, H. D., Vallinoto, A. C. D. R., & Guerreiro, J. (2024) · Infection, Genetics and Evolution · doi:10.1016/j.meegid.2024.105564 · Cited by 8
Aziz, M. A., & Islam, M. S. (2022) · Molecular Genetics & Genomic Medicine · doi:10.1002/mgg3.2063 · Cited by 8 · see citing works
“…during the postCOVID- 19 situation to correlate with the susceptibility of SARS- CoV- 2 infection, associated clinical outcomes, and mortality rate (Çelik et al., 2021; Delanghe et al., 2020; Gómez et al., 2020; Hatami et al., 2020; Pati et al., 2020; Saadat, 2020; Yamamoto et al., 2020).”
BackgroundHuman interaction targets of SARS-CoV-2 spike protein: A systematic review
Faraji, S. N., Raee, M. J., Hashemi, S. M. A., Daryabor, G., Tabrizi, R., Dashti, F. S., Behboudi, E., Heidarnejad, K., Nowrouzi‐Sohrabi, P., & Hatam, G. (2022) · European Journal of Inflammation · doi:10.1177/1721727x221095382 · Cited by 15 · see citing works
Could the CCR5-Δ32 Mutation be Protective in SARS-CoV-2 Infection?
Čizmarević, N. S., Kapović, M., Rončević, D., & Ristić, S. (2021) · Physiological Research · doi:10.33549/physiolres.934725 · Cited by 8
Livshits, L., Harashchenko, T., Umanets, T., Krasnienkov, D. S., Gorodna, O., Podolskiy, V., Kaminska, T., Lapshyn, V., Podolskiy, V., & Antipkin, Y. (2021) · Cytology and Genetics · doi:10.3103/s0095452721050054 · Cited by 8
Illi, B., Vasapollo, B., Valensise, H. C. C., & Totta, P. (2021) · Reproductive Medicine · doi:10.3390/reprodmed2020010 · Cited by 9 · see citing works
“Intriguingly, the II ACE genotype is inversely correlated both to COVID-19 incidence and mortality [95], suggesting the DD genotype as a predisposing factor to develop the disease and confirming hypertension as an underlying clinical condition contributing to the pathogenesis of both COVID-19 and PE.”
MethodOyeleye, S. I., Ojo, O. R., Ajeigbe, A. S., & Oboh, G. (2024) · Comparative Clinical Pathology · doi:10.1007/s00580-024-03611-4 · Cited by 5 · see citing works
“It works by converting angiotensin I into angiotensin II, a potent vasoconstrictor, which helps to increase blood pressure (Yamamoto et al. 2020).”
de Sousa, R. B. N., Nascimento, L. D. D., Costa, L. H. A., Leite, V. R. M. C., Borges, C. L., de Deus, J. M., Rebelo, A., Pinheiro, D. D. S., & Pedrino, G. (2023) · PLoS ONE · doi:10.1371/journal.pone.0288178 · Cited by 7 · see citing works
“Then, an ecological study conducted by Yamamoto et al. (2020) [52] involving data from 26 countries in Europe and Asia reported a negative ACE II genotype correlation with the number of COVID-19 cases (R = − 0.847) and deaths (R = − 0.755).”
BackgroundInfluentialTong, J., Chen, Y., He, M., Wang, W., Wang, Y., Li, N., & Xia, Q. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1190939 · Cited by 7 · see citing works
“Moreover, some researchers hypothesized that regional differences in allele frequencies might explain different incidence and mortality rates (Cao et al., 2020; Yamamoto et al., 2020).”
BackgroundRani, S., & Jain, A. (2023) · Multimedia tools and applications · doi:10.1007/s11042-023-15539-y · Cited by 7 · see citing works
“Another study was done by Yamamoto N et al. (2020) [109] for investigating the involvement of genetic factors linked with SARS-CoV-2 infection.”
Cenanovic, M., Dogan, S., Ašić, A., Bešić, L., & Marjanović, D. (2021) · Genetic Testing and Molecular Biomarkers · doi:10.1089/gtmb.2020.0207 · Cited by 7
Papadopoulos, K., Papadopoulou, A., & Aw, T. (2022) · Human Cell · doi:10.1007/s13577-022-00819-w · Cited by 6 · see citing works
“SNPs involving all the above-mentioned RAAS molecules, (ACE/ACE2/AGT/AGTR1), while protective in malaria, have been implicated in severe adult COVID-19 outcomes (Table 2) [104, 106, 115].”
BackgroundEffects of Human Genetic Factors (Ethnicity and Race) on Clinical Severity of SARS-CoV-2 (COVID-19)
Gökçe, I., Aydemir, K., Ayan, S., Altuntaş, İ., & Erbaş, O. (2021) · Journal of Experimental and Basic Medical Sciences · doi:10.5606/jebms.2020.75631 · Cited by 6 · see citing works
“[17] ACE1 II polymorphism has been found to be associated with lower death and infection rate of SARS-CoV-2 infection.[17] It is determined the European population has a lower frequency of ACE1 II genotype, and this situation might explain higher mortality and prevalence rates of COVID-19 infection in the European reg…”
BackgroundInfluentialAbbaszadeh, H., Kabiri-rad, H., Mohammadi, F., Zangoie, S., Rajabi-Moghaddam, M., Ghafari, S., Ziaee, M., Javanmard, D., & Miri-Moghaddam, E. (2024) · Biochemical Genetics · doi:10.1007/s10528-024-10722-8 · Cited by 5 · see citing works
“Studies performed on Asians showed that the patients with the low DD genotype and a higher II genotype frequency have a statistically significant lower mortality (Pati et al. 2020; Yamamoto et al. 2020; Verma et al. 2021 ).”
Khullar, N., Bhatti, J. S., Singh, S., Thukral, B., Reddy, P., & Bhatti, G. K. (2023) · World Journal of Gastroenterology · doi:10.3748/wjg.v29.i14.2064 · Cited by 5 · see citing works
Li, L., & Murakami, S. (2022) · medRxiv · doi:10.3390/ijms24043411 · Cited by 5 · see citing works
“In addition, the D-allele has been linked with higher mortality rates from COVID-19 [19].”
BackgroundResultBaştuğ, S., Cavdarli, B., Baştuğ, A., Sencan, I., Tuncez, E., Çakir, E., Kemirtlek, N., Sakar, C., Erdem, D., Ceylan, G., et al. (2021) · Anatolian journal of cardiology · doi:10.5152/anatoljcardiol.2021.502 · Cited by 5
“(1) reported that the prevalence of ACE1 II genotype in the population was negatively correlated with the mortality because of COVID-19.”
BackgroundSaid, R., Jenni, R., Boussetta, S., Ammous, F., Zouari, S., Zaghbib, S., Chakroun, M., Derouiche, A., Chebil, M., & Ouerhani, S. (2021) · Journal of clinical laboratory analysis (Print) · doi:10.1002/jcla.24129 · Cited by 5
Singh, H., Nair, A., & Mahajan, S. (2024) · Pathology, Research and Practice · doi:10.1016/j.prp.2024.155608 · Cited by 4 · see citing works
Sahranavard-Pirbazari, P., Khoshghiafeh, A., Kamali, M., Esfandiar, H., Bakhtiari, M., & Ahmadifard, M. (2023) · Advances in Medical Sciences · doi:10.1016/j.advms.2023.10.010 · Cited by 4 · see citing works
Genetic Variants and Protective Immunity against SARS-CoV-2
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“In European and Asian nations, however, greater frequency of the I/I genotype was negatively associated with vulnerability to SARS-CoV-2 infection and subsequent death [73].”
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- 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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