Worldwide ACE (I/D) polymorphism may affect COVID-19 recovery rate: an ecological meta-regression

Abstract

With the emergence of the Novel Coronavirus (2019-nCoV), researchers worldwide have started detecting the probable pathogenesis of the disease. The renin-angiotensin system (RAS) and angiotensin-converting enzymes have received a good deal of attention as possible pathways involved in 2019-nCoV pathogenesis. As the experiments seeking to find potential medications acting on these pathways are being conducted in the early phases, having an ecological worldview on the relationship between the prevalence of COVID-19 disease and the genetic differences in the genes involved in the RAS system could be valuable for the field. In this regard, we conducted a meta-analysis study of the prevalence of ACE (I/D) genotype in countries most affected by the COVID-19. In the meta-analysis, 48,758 healthy subjects from 30 different countries were evaluated in 116 studies, using the Comprehensive Meta-analysis software. The I/D allele frequency ratio was pooled by a random-effect model. The COVID-19 prevalence data of death and recovery rates were evaluated as the latitudes for the meta-regression analysis. Our results demonstrated that with the increase of the I/D allele frequency ratio, the recovery rate significantly increased (point estimate: 0.48, CI 95%: 0.05-0.91, p = 0.027). However, there was no significant difference in the case of death rate (point estimate: 1.74, CI 95%: 4.5-1.04, p = 0.22). This ecological perspective coupled with many limitations does not provide a direct clinical relevance between the COVID-19 and RAS system, but it shows potential pathophysiological associations. Our results raise concerns about ethnic and genetic differences that could affect the effectiveness of the currently investigated RAS-associated medications in different regions.

ACE polymorphism and COVID-19 outcome

“…With interest with read the paper by Hatami et al on angiotensin converting enzyme 1 (ACE1) I/D polymorphism and the recovery rate in COVID-19. Although we agree that genetics play a role in COVID-19 prevalence and mortality [ 1 – 3 ], we disagree with various aspects (quality and representativity of the genotype distribution studies enroled, some epidemiological data) of the statistical analysis, which has been carried out in the paper.…”

Role of comorbidities like diabetes on severe acute respiratory syndrome coronavirus-2: A review

“…ACE2 expression is less frequent in patients with SARS-CoV. Genetic polymorphism may explain why COVID-19 has the highest incidence rate in Europe than in Africa [ [62] , [63] , [64] , [65] ].…”

Understanding COVID-19: From Origin to Potential Therapeutics

“…As discussed earlier, ACE2 is the receptor for SARS-CoV-2. It has been reported that the involvement of ACE2 receptors is also related to the renin-angiotensin system (RAS) in 2019-nCoV pathogenesis [63]. Very recently, a meta-analysis was conducted to get insight into the relationship between the prevalence of COVID-19 disease and the genetic differences in the genes involved in the RAS system [63].…”

“…It has been reported that the involvement of ACE2 receptors is also related to the renin-angiotensin system (RAS) in 2019-nCoV pathogenesis [63]. Very recently, a meta-analysis was conducted to get insight into the relationship between the prevalence of COVID-19 disease and the genetic differences in the genes involved in the RAS system [63]. The results of the study suggest that the increase of the I/D allele frequency ratio significantly increases the recovery rate (point estimate: 0.48, confidence interval (CI) 95%: 0.05-0.91, p = 0.027), but the I/D allele frequency ratio has no significant difference in the case of death rate (point estimate: 1.74, CI 95%: 4.5-1.04, p = 0.22).…”

“…The results of the study suggest that the increase of the I/D allele frequency ratio significantly increases the recovery rate (point estimate: 0.48, confidence interval (CI) 95%: 0.05-0.91, p = 0.027), but the I/D allele frequency ratio has no significant difference in the case of death rate (point estimate: 1.74, CI 95%: 4.5-1.04, p = 0.22). The I/D allele ratio of ACE receptors varies significantly across world regions, accounting for the different recovery rates across regions, but it also raises concerns that ethnic and genetic differences can impact the effectiveness of currently investigated RAS-associated medications in different regions [63].…”