Assessment of ACE1 variants and ACE1/ACE2 expression in COVID-19 patients

Akbari, Mohammadarian; Taheri, Mohammad; Mehrpoor, Golbarg; Eslami, Solat; Hussen, Bashdar Mahmud; Ghafouri‐Fard, Soudeh; Arefian, Noormohammad

doi:10.1016/j.vph.2021.106934

Cited by 17 publications

(20 citation statements)

References 17 publications

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“…Among the studies included in the susceptibility analysis, the control groups of the following studies did not follow Hardy-Weinberg equilibrium (HWE): ACE1 I/D rs4646994/rs1799752 ( Aladag et al, 2021 Sep , Mir et al, 2021 Oct 27 ); ACE2 rs2285666 ( Möhlendick et al, 2021 Oct 1 ); CCR5 rs333 ( Gómez et al, 2020 ); TMPRSS2 rs12329760 ( Taha et al, 2022 Mar 1 ) and TNFA rs1800629 ( Rokni et al, 2022 Apr , Heidari Nia et al, 2022 ). In the severity analysis, HWE did not exist in the control groups of the following studies: ACE1 I/D rs4646994/rs1799752 ( Gong et al, 2021 , Gunal et al, 2021 Jun , Akbari et al, 2022 Feb , Möhlendick et al, 2021 Oct 1 , Kouhpayeh et al, 2021 Nov 17 ); ACE2 rs2285666 ( Martínez-Gómez et al, 2022 Feb , Möhlendick et al, 2021 Oct 1 ); ACE2 rs2106809 ( Cafiero et al, 2021 May , Sabater Molina et al, 2022 ); ACE2 rs2074192 ( Martínez-Gómez et al, 2022 Feb , Sabater Molina et al, 2022 , Wang et al, 2022 Jan ) , IFITM3 rs12252 ( Abbas et al, 2021 Jun 12 ); TMPRSS2 rs12329760 ( Ravikanth et al, 2021 Sep ); TNFA rs1800629 ( Rokni et al, 2022 Apr ) and VDR rs731236 ( Russo et al, 2021 Jun 8 , Abdollahzadeh et al, 2021 Dec ).…”

Section: Resultsmentioning

confidence: 95%

“…The studies for susceptibility analysis included: ACE1 I/D rs4646994/rs1799752 ( Annunziata et al, 2021 Aug 20 , Gong et al, 2021 , Aladag et al, 2021 Sep , Papadopoulou et al, 2022 Mar , Akbari et al, 2022 Feb , Calabrese et al, 2021 Jan , Saad et al, 2021 Dec , Möhlendick et al, 2021 Oct 1 , Gómez et al, 2020 Dec , Hubacek et al, 2021 Aug , Kouhpayeh et al, 2021 Nov 17 , Mahmood et al, 2022 Feb , Mir et al, 2021 Oct 27 ); ACE2 rs2285666 ( Möhlendick et al, 2021 Oct 1 , Alimoradi et al, 2022 Mar 19 , Gómez et al, 2020 Dec , Mahmood et al, 2022 Feb ); APOE rs429358 ( Kuo et al, 2020 May 26 , Al-Jaf et al, 2021 Nov , Hilser et al, 2021 Jan ); CCR5 rs333 ( Cuesta-Llavona et al, 2021 Sep , Bernas et al, 2021 Apr , Gómez et al, 2020 ); IFITM3 rs12252 ( Abbas et al, 2021 Jun 12 , Schönfelder et al, 2021 Jun , Gómez et al, 2021 Jan ); TMPRSS2 rs12329760 ( Taha et al, 2022 Mar 1 , Andolfo et al, 2021 , Schönfelder et al, 2021 Apr , Wulandari et al, 2021 ), and TNFA rs1800629 ( Rokni et al, 2022 Apr , Saleh et al, 2020 Nov , Heidari Nia et al, 2022 ). Severity-wise analysis was performed for ACE1 I/D rs4646994/rs1799752 ( Karakaş Çelik et al, 2021 Oct , Gong et al, 2021 , Gunal et al, 2021 Jun , Martínez-Gómez et al, 2022 Feb , Baştuğ et al, 2021 Dec 8 , Akbari et al, 2022 Feb , Saad et al, 2021 Dec , Möhlendick et al, 2021 Oct 1 , Cafiero et al, 2021 May , Gómez et al, 2020 Dec , Hubacek et al, 2021 Aug , Kouhpayeh et al, 2021 Nov 17 , Mahmood et al, 2022 Feb , Mir et al, 2021 Oct 27 ...…”

Section: Resultsmentioning

confidence: 99%

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Systematic review and meta-analysis of human genetic variants contributing to COVID-19 susceptibility and severity

Gupta

Kaur²,

Pathak³

et al. 2022

Gene

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Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Systematic review and meta-analysis of human genetic variants contributing to COVID-19 susceptibility and severity

Gupta

Kaur²,

Pathak³

et al. 2022

Gene

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“…The protective effect of this allele was also reported in COVID-19 patients from Lebanon and India (Saad et al, 2021[ 45 ]; Verma et al, 2021[ 53 ]). Contrary to these results, Karakaş Çelik et al (2021[ 26 ]), Möhlendick et al (2021[ 34 ]) and Akbari et al (2022[ 2 ]) failed to confirm a supposed association between rs1799752 and disease severity. In their study conducted on Saudi Arabian patients, Mir et al (2021[ 33 ]) claimed that minor allele I has protective effect against disease severity.…”

Section: Discussionmentioning

confidence: 92%

“…Basic characteristics of the remaining 29 studies (Abdollahzadeh et al, 2021[ 1 ]; Aladag et al, 2021[ 4 ]; Al-Anouti et al, 2021[ 5 ]; Alghamdi et al, 2021[ 6 ]; Akbari et al, 2022[ 2 ]; Akin et al, 2022[ 3 ]; Apaydin et al, 2022[ 7 ]; Cafiero et al, 2021[ 10 ]; Karakaş Çelik et al, 2021[ 26 ]; Cuesta-Llavona et al, 2021[ 13 ]; Gómez et al, 2020[ 20 ]; Gómez et al, 2021[ 19 ]; Gunal et al, 2021[ 21 ]; Hubacek et al, 2021[ 23 ]; Íñiguez et al, 2021[ 24 ]; Kotur et al, 2021[ 27 ]; Kouhpayeh et al, 2021[ 28 ]; Mir et al, 2021[ 33 ]; Möhlendick et al, 2021[ 34 ]; Monticelli et al, 2021[ 35 ]; Novelli et al, 2020[ 36 ]; Peralta et al, 2021[ 39 ]; Ravikanth et al, 2021[ 43 ]; Saad et al, 2021[ 45 ]; Schönfelder et al, 2021[ 49 ][ 48 ]; Verma et al, 2021[ 53 ]; Wang et al, 2022[ 55 ]; Wulandari et al, 2021[ 57 ]; Zhang et al, 2020[ 59 ]), with a total number of 8247 SARS-CoV-2-positive participants, included in qualitative data synthesis, are given in Table 1 (Tab. 1) (References in Table 1: Abdollahzadeh et al, 2021[ 1 ]; Akbari et al, 2022[ 2 ]; Akin et al, 2022[ 3 ]; Aladag et al, 2021[ 4 ]; Al-Anouti et al, 2021[ 5 ]; Alghamdi et al, 2021[ 6 ]; Apaydin et al, 2022[ 7 ]; Cafiero et al, 2021[ 10 ]; Cuesta-Llavona et al, 2021[ 13 ]; Gómez et al , 2020[ 20 ], 2021[ 19 ]; Gunal et al, 2021[ 21 ]; Hubacek et al, 2021[ 23 ]; Íñiguez et al, 2021[ 24 ]; Karakaş Çelik et al, 2021[ 26 ]; Kotur et al, 2021[ 27 ]; Kouhpayeh et al, 2021;[ 28 ] Mir et al, 2021[ 33 ]; Möhlendick et al, 2021[ 34 ]; Monticelli et al, 2021[ …”

Section: Resultsmentioning

confidence: 99%

“…However, not all of them were included in quantitative data synthesis, since one study (Íñiguez et al, 2021[ 24 ]) investigated variants other than the most common rs1799752. Furthermore, data on ACE1 polymorphism reported in three studies could not be combined with the results from other articles, due to differences in stratification criteria applied to define patients' groups (Akbari et al, 2022[ 2 ]; Cafiero et al, 2021[ 10 ]; Hubacek et al, 2021[ 23 ]).…”

Section: Resultsmentioning

confidence: 99%

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

Dobrijević

Robajac

Gligorijević

et al. 2022

EXCLI Journal; 21:Doc818; ISSN 1611-2156

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Genes involved in the regulation of viral recognition and its entry into a host cell have been identified as candidates for genetic association studies on COVID-19 severity. Published findings on the effects of polymorphisms within ACE1 , ACE2 , TMPRSS2 , IFITM3 and VDR genes remained inconclusive, so we conducted a systematic review and meta-analysis in order to elucidate their potential involvement in the genetic basis underlying the severity of COVID-19 and/or an outcome of SARS-CoV-2 infection. Identification of potentially eligible studies was based on PubMed, Scopus and Web of Science database search. Relevant studies (n=29) with a total number of 8247 SARS-CoV-2-positive participants were included in qualitative synthesis, while results of 21 studies involving 5939 were pooled in meta-analysis. Minor allele I of rs1799752 located within ACE1 was identified as a protective variant against severe COVID-19, while its effect on mortality rate was opposite. Similarly, minor allele A of ACE2 polymorphism, rs2285666, was found to associate with a decreased risk of severe COVID-19 ( P = 0.003, OR = 0.512, 95 % CI = 0.331-0.793). Statistical significance was also seen for the association between COVID-19 severity and rs12329760 located within TMPRSS2 . Our results did not support the supposed association of rs12252 in IFITM3 and polymorphisms within VDR with disease severity. We conclude that genetic variants within ACE1 , ACE2 and TMPRSS2 may be potential biomarkers of COVID-19 severity, which needs to be further confirmed in a larger set of studies.

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

Aziz

Islam

2022

Molec Gen & Gen Med

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Background ACE1 I/D rs1799752 and ACE2 rs2285666 genetic polymorphisms could play a critical role in altering the clinical outcomes of SARS‐CoV‐2. The findings of previous studies remained inconclusive. This meta‐analysis was performed to evaluate the association and provide a more reliable outcome. Methods This study was completed following the updated recommendations of PRISMA using RevMan 5.4.1 statistical software. Results A total of 11 studies with 950 severe cases and 1573 non‐severe cases with COVID‐19 infection were included. Pooled analysis showed that ACE1 I/D polymorphism was correlated with the severity of SARS‐CoV‐2 in the DD genotype and D allele for the fixed‐effects model (OR:1.27 and OR:1.17). Besides, codominant 3, recessive, and allele models were associated with the severity of the fixed‐effects model (OR:1.35, OR:1.37, and OR:1.20) in Caucasian ethnicity. ACE2 rs2285666 was linked with the severity in codominant 3 (OR:2.63, for both random‐ and fixed effects‐models), overdominant (OR:1.97, for random‐effects model and OR:1.97, for fixed effects‐model), and recessive model (OR:0.41 for fixed‐ and random‐effects model). Allele model of rs2285666 showed a significant association in the fixed‐effects model (OR:1.61). Conclusion Our present meta‐analysis suggests that ACE1 I/D rs1799752 and ACE2 rs2285666 variants may enhance the severity in SARS‐CoV‐2 infected patients. Future studies are warranted to verify our findings.

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Assessment of ACE1 variants and ACE1/ACE2 expression in COVID-19 patients

Cited by 17 publications

References 17 publications

Systematic review and meta-analysis of human genetic variants contributing to COVID-19 susceptibility and severity

Systematic review and meta-analysis of human genetic variants contributing to COVID-19 susceptibility and severity

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

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

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