ACE I/D polymorphism and epidemiological findings for COVID-19: One year after the pandemic outbreak in Europe.

We have read with great interest several recent articles on the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene and its potential relevance to the risk of a SARS-CoV-2 infection and the severity of the consequent coronavirus disease 2019 (COVID-19).1Delanghe J.R. Speeckaert M.M. De Buyzere M.L The host's angiotensin-converting enzyme polymorphism may explain epidemiological findings in COVID-19 infections.Clin Chim Acta. 2020; 505: 192-193https://doi.org/10.1016/j.cca.2020.03.031.2Crossref PubMed Scopus (0) Google Scholar, 2Delanghe J.R. Speeckaert M.M. De Buyzere M.L COVID-19 infections are also affected by human ACE1 D/I polymorphism.Clin Chem Lab Med. 2020; 58: 1125-1126https://doi.org/10.1515/cclm-2020-0425.3Crossref PubMed Scopus (0) Google Scholar, 3Yamamoto N. Ariumi Y. Nishida N. Yamamoto R. Bauer G. Gojobori T. et al.SARS-CoV-2 infections and COVID-19 mortalities strongly correlate with ACE1 I/D genotype.Gene. 2020; 758144944https://doi.org/10.1016/j.gene.2020.144944Crossref PubMed Scopus (21) Google Scholar, 4Cenanovic M. Dogan S. Asic A. Besic L. Marjanovic D. Distribution of the ACE1 D allele in the bosnian-herzegovinian population and its possible role in the regional epidemiological picture of COVID-19.Genet Test Mol Biomarkers. 2021; 25: 55-58https://doi.org/10.1089/gtmb.2020.0207Crossref PubMed Scopus (0) Google Scholar, 5Bellone M. Calvisi S.L. ACE polymorphisms and COVID-19-related mortality in Europe.J Mol Med (Berl). 2020; 98: 1505-1509https://doi.org/10.1007/s00109-020-01981-0Crossref PubMed Scopus (6) Google Scholar, 6Aung A.K. Aitken T. Teh B.M. Yu C. Ofori-Asenso R. Chin K.L. et al.Angiotensin converting enzyme genotypes and mortality from COVID-19: an ecological study.J Infect. 2020; 81: 961-965https://doi.org/10.1016/j.jinf.2020.11.012.7Crossref PubMed Scopus (0) Google Scholar These epidemiological studies, which analyzed either European populations1Delanghe J.R. Speeckaert M.M. De Buyzere M.L The host's angiotensin-converting enzyme polymorphism may explain epidemiological findings in COVID-19 infections.Clin Chim Acta. 2020; 505: 192-193https://doi.org/10.1016/j.cca.2020.03.031.2Crossref PubMed Scopus (0) Google Scholar, 5Bellone M. Calvisi S.L. ACE polymorphisms and COVID-19-related mortality in Europe.J Mol Med (Berl). 2020; 98: 1505-1509https://doi.org/10.1007/s00109-020-01981-0Crossref PubMed Scopus (6) Google Scholar, 6Aung A.K. Aitken T. Teh B.M. Yu C. Ofori-Asenso R. Chin K.L. et al.Angiotensin converting enzyme genotypes and mortality from COVID-19: an ecological study.J Infect. 2020; 81: 961-965https://doi.org/10.1016/j.jinf.2020.11.012.7Crossref PubMed Scopus (0) Google Scholar or global populations that included Europe,2Delanghe J.R. Speeckaert M.M. De Buyzere M.L COVID-19 infections are also affected by human ACE1 D/I polymorphism.Clin Chem Lab Med. 2020; 58: 1125-1126https://doi.org/10.1515/cclm-2020-0425.3Crossref PubMed Scopus (0) Google Scholar, 3Yamamoto N. Ariumi Y. Nishida N. Yamamoto R. Bauer G. Gojobori T. et al.SARS-CoV-2 infections and COVID-19 mortalities strongly correlate with ACE1 I/D genotype.Gene. 2020; 758144944https://doi.org/10.1016/j.gene.2020.144944Crossref PubMed Scopus (21) Google Scholar, 4Cenanovic M. Dogan S. Asic A. Besic L. Marjanovic D. Distribution of the ACE1 D allele in the bosnian-herzegovinian population and its possible role in the regional epidemiological picture of COVID-19.Genet Test Mol Biomarkers. 2021; 25: 55-58https://doi.org/10.1089/gtmb.2020.0207Crossref PubMed Scopus (0) Google Scholar have reported conflicting results (Table 1). Variability in results may arise, due to various factors, including differences in the ethnicities/countries included in the analysis, which might reflect differences in genetic background; differences in other biological, environmental, and social risk parameters; and differences in the prevalence of the ACE I/D polymorphism. Indeed, it is well documented that the frequency of the ACE-D allele varies according to the ethnic/geographic origin of the study cohort. The prevalence of the ACE-D allele increases from Eastern to Western countries, worldwide. The prevalence in Asian populations (approximately 25–40%) is lower than the prevalence in Caucasian (generally approximately 40–60%) and African (60%) populations. Therefore, we focused our interest on studies that analyzed the European region, which also provided conflicting results, despite the similarities among these populations, in terms of ancestry, other risk covariates for COVID-19, and strategies for controlling the pandemic.Table 1Epidemiological studies on associations between ACE I/D polymorphisms and COVID-19 prevalence/mortality.Author (reference)Geographic regionDate assessedACE I/D allele/genotypeAssociation with COVID-19 prevalence and/or mortalityDelanghe (1)Europe (25 countries)20 March 2020D allelenegative associationDelanghe (2)European (26 countries), North African and Middle Eastern countries1 April 2020D allelenegative associationYamamoto (3)European (19 countries), Middle Eastern, South Asian, and East Asian countries23 May 2020II genotypenegative associationAung (4)Worldwide countries (9 European)8 June 2020DD genotypeno associationII genotypenegative associationCenanovic (5)Europe (18 countries)10 July 2020D alleleno associationBellone (6)Europe (24 countries)5 August 2020DD genotypepositive associationII genotypenegative association Open table in a new tab