Genetic polymorphisms of ACE1, ACE2, and TMPRSS2 associated with COVID‐19 severity: A systematic review with meta‐analysis

Saengsiwaritt, Wacharapol; Jittikoon, Jiraphun; Chaikledkaew, Usa; Udomsinprasert, Wanvisa

doi:10.1002/rmv.2323

Cited by 54 publications

(55 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recently, two meta-analyses evaluated the influence of the polymorphisms in ACE1 , ACE2 , and TMPRSS2 ( Deb et al, 2022 Apr ) and ACE1 ; IFITM3 , FURIN , and TNF

( Saengsiwaritt et al, 2022 Jan ) on susceptibility to SARS-CoV-2 infection. However, these studies represented only a subset of potential genetic biomarkers that have been assessed for conferring risk to COVID-19.…”

Section: Discussionmentioning

confidence: 99%

“…The rest of the polymorphisms lacked sufficient number of studies to conduct statistical analysis of association. We performed updated meta-analyses for the polymorphisms that were evaluated for association with COVID-19 in the previous meta-analyses ( Deb et al, 2022 Apr , Saengsiwaritt et al, 2022 Jan ). Our study unveiled statistically significant associations between the polymorphisms ACE1 I/D rs1799752/rs4646994, APOE rs429358, CCR5 rs333, and IFITM3 rs12252 and susceptibility to SARS-CoV-2 infection.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Gupta

Kaur²,

Pathak³

et al. 2022

Gene

View full text Add to dashboard Cite

“…Recently, two meta-analyses evaluated the influence of the polymorphisms in ACE1 , ACE2 , and TMPRSS2 ( Deb et al, 2022 Apr ) and ACE1 ; IFITM3 , FURIN , and TNF

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

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

View full text Add to dashboard Cite

“…Moreover, it has been associated with poor clinical outcomes of acute respiratory distress syndrome (ARDS), where individuals with the D/D genotype had significantly higher mortality than those who carry the I/I genotype ( 12 ). In addition, different reports have proposed that ACE2 polymorphisms rs2285666 (G870A) could modulate the susceptibility to SARS-CoV-2 infection by contributing to higher expression of ACE2 receptor ( 13 , 14 ).…”

Section: Introductionmentioning

confidence: 99%

ACE and ACE2 Gene Variants Are Associated With Severe Outcomes of COVID-19 in Men

et al. 2022

View full text Add to dashboard Cite

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic, affecting more than 219 countries and causing the death of more than 5 million people worldwide. The genetic background represents a factor that predisposes the way the host responds to SARS-CoV-2 infection. In this sense, genetic variants of ACE and ACE2 could explain the observed interindividual variability to COVID-19 outcomes. In order to improve the understanding of how genetic variants of ACE and ACE2 are involved in the severity of COVID-19, we included a total of 481 individuals who showed clinical manifestations of COVID-19 and were diagnosed by reverse transcription PCR (RT-PCR). Genomic DNA was extracted from peripheral blood and saliva samples. ACE insertion/deletion polymorphism was evaluated by the high-resolution melting method; ACE single-nucleotide polymorphism (SNP) (rs4344) and ACE2 SNPs (rs2285666 and rs2074192) were genotyped using TaqMan probes. We assessed the association of ACE and ACE2 polymorphisms with disease severity using logistic regression analysis adjusted by age, sex, hypertension, type 2 diabetes, and obesity. The severity of the illness in our study population was divided as 31% mild, 26% severe, and 43% critical illness; additionally, 18% of individuals died, of whom 54% were male. Our results showed in the codominant model a contribution of ACE2 gene rs2285666 T/T genotype to critical outcome [odds ratio (OR) = 1.83; 95%CI = 1.01–3.29; p = 0.04] and to require oxygen supplementation (OR = 1.76; 95%CI = 1.01–3.04; p = 0.04), in addition to a strong association of the T allele of this variant to develop critical illness in male individuals (OR = 1.81; 95%CI = 1.10–2.98; p = 0.02). We suggest that the T allele of rs2285666 represents a risk factor for severe and critical outcomes of COVID-19, especially for men, regardless of age, hypertension, obesity, and type 2 diabetes.

show abstract

“…Two polymorphisms analyzed in our study, ACE rs4646994 and ACE2 rs2285666, are important regulators of the RAAS pathway, a physiological system implicated in COVID-19 susceptibility and severity ( 92 ). Despite we did not find evidence of association between these polymorphisms and COVID-19 severity, numerous studies support a biological basis for such relationship ( 92 – 94 ). The ACE2 rs2285666 T allele is associated with a significant increase in ACE2 expression ( 95 ).…”

Section: Discussionmentioning

confidence: 99%

Association Between the LZTFL1 rs11385942 Polymorphism and COVID-19 Severity in Colombian Population

et al. 2022

View full text Add to dashboard Cite

Genetic and non-genetic factors are responsible for the high interindividual variability in the response to SARS-CoV-2. Although numerous genetic polymorphisms have been identified as risk factors for severe COVID-19, these remain understudied in Latin-American populations. This study evaluated the association of non-genetic factors and three polymorphisms: ACE rs4646994, ACE2 rs2285666, and LZTFL1 rs11385942, with COVID severity and long-term symptoms by using a case-control design. The control group was composed of asymptomatic/mild cases (n = 61) recruited from a private laboratory, while the case group was composed of severe/critical patients (n = 63) hospitalized in the Hospital Universitario Mayor-Méderi, both institutions located in Bogotá, Colombia. Clinical follow up and exhaustive revision of medical records allowed us to assess non-genetic factors. Genotypification of the polymorphism of interest was performed by amplicon size analysis and Sanger sequencing. In agreement with previous reports, we found a statistically significant association between age, male sex, and comorbidities, such as hypertension and type 2 diabetes mellitus (T2DM), and worst outcomes. We identified the polymorphism LZTFL1 rs11385942 as an important risk factor for hospitalization (p < 0.01; OR = 5.73; 95% CI = 1.2–26.5, under the allelic test). Furthermore, long-term symptoms were common among the studied population and associated with disease severity. No association between the polymorphisms examined and long-term symptoms was found. Comparison of allelic frequencies with other populations revealed significant differences for the three polymorphisms investigated. Finally, we used the statistically significant genetic and non-genetic variables to develop a predictive logistic regression model, which was implemented in a Shiny web application. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC = 0.86; 95% confidence interval 0.79–0.93). These results suggest that LZTFL1 rs11385942 may be a potential biomarker for COVID-19 severity in addition to conventional non-genetic risk factors. A better understanding of the impact of these genetic risk factors may be useful to prioritize high-risk individuals and decrease the morbimortality caused by SARS-CoV2 and future pandemics.

show abstract

Genetic polymorphisms of ACE1, ACE2, and TMPRSS2 associated with COVID‐19 severity: A systematic review with meta‐analysis

Cited by 54 publications

References 50 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

ACE and ACE2 Gene Variants Are Associated With Severe Outcomes of COVID-19 in Men

Association Between the LZTFL1 rs11385942 Polymorphism and COVID-19 Severity in Colombian Population

Contact Info

Product

Resources

About