ACE gene I/D polymorphism and severity of SARS-CoV-2 infection in hospitalized patients: a meta-analysis

Abstract

Background: Hypertension and type 2 diabetes increase the risk of severe SARS-CoV-2 infection. On the other hand, homozygous ACE deletion polymorphism (DD) has been associated with these two diseases and risk of acute respiratory distress syndrome. The aim of the study was to conduct a meta-analysis of the association between ACE gene I/D polymorphism (DD, II and DI) and severity of SARS-CoV-2 infection in hospitalized patients. Material and methods: We searched PubMed, EMBASE and Google Scholar for studies published between January 2020 and April 2021. We included case-control studies evaluating the association between ACE I/D and severity of SARS-CoV-2 infection in hospitalized patients, were there was sufficient genotype or allele frequency data to calculate IRR (incidence rate ratio) and 95% confidence intervals (CIs). Results: Five studies were included (mean age 58.5 years and 61% men), combining to a total of 786 patients. Four studies were conducted in Caucasians. Overall, patients who had homozygous co-dominance genotype DD were at 47% higher risk of severe COVID-19 compared with II or ID (IRR: 1.47; 95% CI: 1.15-1.89; p = 0.002). Conclusions:The ACE DD genotype may confer a greater risk of severe COVID-19 in hospitalized patients. Further studies including more diverse ethnic groups are necessary to fully establish this association.

The association of ACE1, ACE2, TMPRSS2, IFITM3 and VDR polymorphisms with COVID-19 severity: a systematic review and meta-analysis

“…However, authors made a major error in their data-synthesis by not recognizing rs1799752 and rs4646994 as synonyms for the same genetic variant and, therefore, excluding several eligible studies from the pooled analysis. Our results are also consistent with those obtained by Oscanoa et al (2021[ 37 ]) in their meta-analysis which included only five studies on the effects of rs1799752 and different patient classification criteria.…”

“…The main objective of the present study is to elucidate effects of naturally occurring variants within ACE1 , ACE2 , TMPRSS2 , IFITM3 and VDR genes on clinical severity of COVID-19 and/or the outcome of SARS-CoV-2 infection. Since two previous meta-analyses (Oscanoa et al, 2021[ 37 ]; Saengsiwaritt et al, 2022[ 46 ]) investigated the effect of ACE1 indel polymorphism, we conducted an updated pooled analysis aiming to provide a more accurate assessment. Justification for the present study may be seen in the inclusion of almost twice as many articles on the effects of ACE1 polymorphisms, compared to the recent meta-analysis (Saengsiwaritt et al, 2022[ 46 ]).…”

Severity of coronavirus disease 19: Profile of inflammatory markers and ACE (rs4646994) and ACE2 (rs2285666) gene polymorphisms in Iraqi patients

“…Regarding hypertension and diabetes and prior to the COVID-19 pandemic, three meta-analysis studies considered the D allele of the rs4646994 SNP as a risk variant for developing hypertension or diabetes in various world populations including Asian, Caucasian and African populations ( Oscanoa et al, 2021 ). In the current study, this role for the D allele was not confirmed and no significant differences were found in the distribution of allele or genotype frequencies of rs4646994 polymorphism between diabetic and non-diabetic or hypertensive and non-hypertensive COVID-19 patients.…”

Association of ACE1 I/D rs1799752 and ACE2 rs2285666 polymorphisms with the infection and severity of COVID‐19: A meta‐analysis

“…Based on the recommendations for establishing more compact scientific evidence by Oscanoa et al ( 2021 ), we performed the present meta‐analysis to explore the association of ACE1 and ACE2 genetic polymorphisms with the severity of SARS‐CoV‐2 infected patients. Our current meta‐analysis suggests that ACE1 I/D rs1799752 and ACE2 rs2285666 variants may increase the severity in SARS‐CoV‐2‐infected patients.…”

“…Although Oscanoa et al ( 2021 ) performed the first meta‐analysis with ACE1 I/D polymorphism, we have performed the first meta‐analysis, including ACE1 I/D rs1799752 and ACE2 rs2285666 variants. Besides, we have included comparatively large number studies (11 studies) with ACE1 I/D polymorphism (severe cases = 758 and non‐severe cases = 1109), with ACE2 rs2285666 polymorphism (severe cases = 192, non‐severe cases = 464) that includes population from both Caucasian and Asian ancestry.…”