Ethnic Prevalence of Angiotensin-Converting Enzyme Deletion (D) Polymorphism and COVID-19 Risk: Rationale for Use of Ang
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Ethnic Prevalence of Angiotensin-Converting Enzyme Deletion (D) Polymorphism and COVID-19 Risk: Rationale for Use of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers Rangaprasad Sarangarajan 1
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1
3
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& Robert Winn & Michael A. Kiebish & Chas Bountra & Elder Granger & Niven R. Narain
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Received: 2 May 2020 / Revised: 5 August 2020 / Accepted: 24 August 2020 # The Author(s) 2020
Abstract Rationale Hypertension, obesity and diabetes are major risk factors associated with morbidities underlying COVID-19 infections. Regression analysis correlated presence of ACE insertion/deletion (I/D) polymorphism to COVID-19 incidence and mortality. Furthermore, COVID-19 prevalence correlated to allele frequency of angiotensin-converting enzyme (ACE) deletion (D) polymorphism within the European population. Objective Homozygous ACE deletion polymorphism is associated with increase in ACE and angiotensin II (Ang-II), sustained levels can result in inflammation, fibrosis and organ damage. The ACE DD polymorphism is also associated with hypertension, acute respiratory distress and diabetic nephropathy, all considered high risk for COVID-19 infection and outcomes. The study objective was to describe a biological framework associating ethnic prevalence of ACE deletion polymorphism to COVID-19 comorbidities providing rationale for therapeutic utility of ACE-I/ARBs to improve outcomes. Method and Results The Allele Frequency Database (ALFRED) was queried for frequency of rs4646994 representing ACE I/D polymorphism. In a total of 349 worldwide population samples, frequency of ACE D allele was higher in European, Asian, and Africans cohorts. In the USA, the frequency of ACE D allele was higher in non-Hispanic Black compared with non-Hispanic White and Mexican Americans. Conclusion COVID-19 binding mediated reduction/inactivation of ACE-II can increase ACE/Ang-II signalling pathway and related pathologies. The presence of ACE DD polymorphism with COVID-19 infection likely augments ACE/Ang-II activities, increasing severity of COVID-19 morbidities and impacts outcomes. Thus, ethnic prevalence of ACE DD polymorphism can explain in part the severity of COVID-19 morbidity providing rationale for the use of ACE-I/ARBs to improve outcomes. Keywords Angiotensin . ACE . Polymorphism . Ethnic . COVID-19
Introduction The SARS-CoV-19 (COVID-19) infection has infected in excess of seventeen million individuals around the globe and is designated as a pandemic by the World Health Organization. * Rangaprasad Sarangarajan [email protected] 1
BERG LLC, 500 Old Connecticut Path, Bldg B, 3r Floor, Framingham, MA 01701, USA
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Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA
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Center for Medicines Discovery, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX37DQ, UK
The global efforts are focused on understanding the disease onset, progression and to identify causal linkage for differences in observed outcomes among the affected population and within s
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