Ethnic Prevalence of Angiotensin-Converting Enzyme Deletion (D) Polymorphism and COVID-19 Risk: Rationale for Use of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers

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.

Racial and Ethnic Disparities in Years of Potential Life Lost Attributable to COVID-19 in the United States: An Analysis of 45 States and the District of Columbia

“…For example, Blacks and Hispanics in the U.S. have higher rates of underlying medical conditions such as diabetes, hypertension, and obesity [ 75 , 76 ], which have been established as definitive or probable risk factors of severe illness as a result of COVID-19 infection [ 77 ], and it has been hypothesized that the high prevalence of these conditions among Blacks and Hispanics in the U.S. contributes in large part to the observed disparities. Genetic factors have also been speculated as playing a role in the excess mortality experienced by Blacks in particular [ 78 , 79 , 80 ]. However, given that racial/ethnic disparities in the COVID-19 mortality burden reflect disparities in both the risk of COVID-19 infection and the risk of severe illness given COVID-19 infection, the underlying causes of the racial/ethnic disparities in the COVID-19 mortality burden are likely multi-faceted, comprising a complex and interactive combination of factors, including the prevalence of pre-existing comorbid conditions and potentially genetic factors.…”

Racial and Ethnic Disparities in Years of Potential Life Lost Attributable to COVID-19 in the United States: An Analysis of 45 States and the District of Columbia

“…For example, Blacks and Hispanics in the U.S. have higher rates of underlying medical conditions such as diabetes, hypertension, and obesity [66,67], which have been established as definitive or probable risk factors of severe illness as a result of COVID-19 infection [68], and it has been hypothesized that the high prevalence of these conditions among Blacks and Hispanics in the U.S. contributes in large part to the observed disparities. Genetic factors have also been speculated as playing a role in the excess mortality experienced by Blacks in particular [69][70][71]. However, given that racial/ethnic disparities in the COVID-19 mortality burden reflect disparities in both the risk of COVID-19 infection and the risk of severe illness given COVID-19 infection, the underlying causes of the racial/ethnic disparities in the COVID-19 mortality burden are likely multi-faceted, comprising a complex and interactive combination of factors, including the prevalence of pre-existing comorbid conditions and potentially genetic factors.…”

ACE gene variants rise the risk of severe COVID-19 in patients with hypertension, dyslipidemia or diabetes. A pilot study

“…However, we did not observe a higher mean age or a higher prevalence of hypertension, dyslipidemia, diabetes mellitus, obesity and cardiovascular disease in patients admitted to the ICU compared to those admitted to the ward, suggesting that other mechanisms/pathways could be involved in the severity of COVID-19 illness. 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)(21)(22). Thus, we investigated the association of two ACE polymorphisms involved in diabetes and hypertension (rs4341 and rs4343) (7, 8) with COVID-19 outcome in patients from La Rioja.…”