ACE2 polymorphisms impact COVID-19 severity in obese patients

Jalaleddine, Nour; Bouzid, Amal; Hachim, Mahmood Y.; Sharif-Askari, Narjes Saheb; Mahboub, Bassam; Senok, Abiola; Halwani, Rabih; Hamoudi, Rifat; Heialy, Saba Al

doi:10.1038/s41598-022-26072-7

Cited by 8 publications

(6 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rs879922 is found at a lower frequency in African (45%) individuals compared to Europeans (65%). Jalaleddine et al (2022) showed that rs879922 was associated with COVID-19 in obese compared to lean individuals (p = 0.06), which may increase COVID-19 disease severity [111]. In addition, rs2048683 (T>G) was associated with T2D in East Asians [111] and blood pressure in European individuals (2020).…”

Section: Inclusion and Exclusion Criteria For Selected Snpsmentioning

confidence: 99%

“…Jalaleddine et al (2022) showed that rs879922 was associated with COVID-19 in obese compared to lean individuals (p = 0.06), which may increase COVID-19 disease severity [111]. In addition, rs2048683 (T>G) was associated with T2D in East Asians [111] and blood pressure in European individuals (2020). Elbadri et al (2022) reported that the GG genotype (OR 5.852) is a potential marker for the risk of severe SARS-CoV-2 infection within Egyptian individuals [112].…”

Section: Inclusion and Exclusion Criteria For Selected Snpsmentioning

confidence: 99%

See 1 more Smart Citation

Genetic Variants within SARS-CoV-2 Human Receptor Genes May Contribute to Variable Disease Outcomes in Different Ethnicities

Adimulam

Arumugam

Gokul

et al. 2023

IJMS

View full text Add to dashboard Cite

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a global pandemic, with an alarming infectivity and mortality rate. Studies have examined genetic effects on SARS-CoV-2 disease susceptibility and severity within Eurasian populations. These studies identified contrasting effects on the severity of disease between African populations. Genetic factors can explain some of the diversity observed within SARS-CoV-2 disease susceptibility and severity. Single nucleotide polymorphisms (SNPs) within the SARS-CoV-2 receptor genes have demonstrated detrimental and protective effects across ethnic groups. For example, the TT genotype of rs2285666 (Angiotensin-converting enzyme 2 (ACE2)) is associated with the severity of SARS-CoV-2 disease, which is found at higher frequency within Asian individuals compared to African and European individuals. In this study, we examined four SARS-CoV-2 receptors, ACE2, Transmembrane serine protease 2 (TMPRSS2), Neuropilin-1 (NRP1), and Basigin (CD147). A total of 42 SNPs located within the four receptors were reviewed: ACE2 (12), TMPRSS2 (10), BSG (CD147) (5), and NRP1 (15). These SNPs may be determining factors for the decreased disease severity observed within African individuals. Furthermore, we highlight the absence of genetic studies within the African population and emphasize the importance of further research. This review provides a comprehensive summary of specific variants within the SARS-CoV-2 receptor genes, which can offer a better understanding of the pathology of the SARS-CoV-2 pandemic and identify novel potential therapeutic targets.

show abstract

Section: Inclusion and Exclusion Criteria For Selected Snpsmentioning

confidence: 99%

Section: Inclusion and Exclusion Criteria For Selected Snpsmentioning

confidence: 99%

Genetic Variants within SARS-CoV-2 Human Receptor Genes May Contribute to Variable Disease Outcomes in Different Ethnicities

Adimulam

Arumugam

Gokul

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…The genomic data were processed using an in-house bioinformatics pipeline including alignment to the reference genome, quality control evaluation, variant calling and variant annotation as previously described (11). Coverage analysis was applied to the flanking sequences at the gene level of the target regions.…”

Section: Genomic Data Processing and Variant Identificationmentioning

confidence: 99%

“…Most of the 15 variants had higher allele frequency (AF) in the ChinaMAP dataset and EAS populations compared to European populations [10]. Polyphen-2 tool was utilized for its ability to predict the effect of a variant on the resultant protein for the selected 15 variants [11]. Six variants appeared to have a potentially damaging effect on ACE2 protein: S19P, G211R, P263S, S692P, A501T, and L731F.…”

Section: Key Variants In the Ace2 Receptormentioning

confidence: 99%

Association of specific ACE2 and TMPRSS2 variants with circulatory cytokines of COVID-19 Emirati patients

Elemam,

Bouzid,

Alsafar

et al. 2024

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

IntroductionThe COVID-19 pandemic represented one of the most significant challenges to researchers and healthcare providers. Several factors determine the disease severity, whereas none alone can explain the tremendous variability. The Single nucleotide variants (SNVs) in angiotensin-converting enzyme-2 (ACE2) and transmembrane serine protease type-2 (TMPRSS2) genes affect the virus entry and are considered possible risk factors for COVID-19.MethodsWe compiled a panel of gene variants from both genes and used in-silico analysis to predict their significance. We performed biological validation to assess their capacity to alter the ACE2 interaction with the virus spike protein. Subsequently, we conducted a retrospective comparative genome analysis on those variants in the Emirati patients with different disease severity (total of 96) along with 69 healthy control subjects.ResultsOur results showed that the Emirati population lacks the variants that were previously reported as associated with disease severity, whereas a new variant in ACE2 “Chr X:g.15584534” was associated with disease severity specifically among female patients. In-silico analysis revealed that the new variant can determine the ACE2 gene transcription. Several cytokines (GM-CSF and IL-6) and chemokines (MCP-1/CCL2, IL-8/CXCL8, and IP-10/CXCL10) were markedly increased in COVID-19 patients with a significant correlation with disease severity. The newly reported genetic variant of ACE2 showed a positive correlation with CD40L, IL-1β, IL-2, IL-15, and IL-17A in COVID-19 patients.ConclusionWhereas COVID-19 represents now a past pandemic, our study underscores the importance of genetic factors specific to a population, which can influence both the susceptibility to viral infections and the level of severity; subsequently expected required preparedness in different areas of the world.

show abstract

“…We have previously shown that bronchial epithelial cells of obese patients express higher levels of ACE2 , which may explain the increased susceptibility to infection and severe outcomes in obese patients [ 7 ]. We further highlighted how obesity-associated ACE2 polymorphisms may enhance COVID-19 severity in obese patients [ 8 ]. Of note, obesity is associated with chronic systemic inflammation.…”

Section: Introductionmentioning

confidence: 99%

Lung Epithelial Cells from Obese Patients Have Impaired Control of SARS-CoV-2 Infection

Gaudet

Kaufmann

Jalaleddine

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

Obesity is known to increase the complications of the COVID-19 coronavirus disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the exact mechanisms of SARS-CoV-2 infection in obese patients have not been clearly elucidated. This study aims to better understand the effect of obesity on the course of SARS-CoV-2 infection and identify candidate molecular pathways involved in the progression of the disease, using an in vitro live infection model and RNA sequencing. Results from this study revealed the enhancement of viral load and replication in bronchial epithelial cells (NHBE) from obese subjects at 24 h of infection (MOI = 0.5) as compared to non-obese subjects. Transcriptomic profiling via RNA-Seq highlighted the enrichment of lipid metabolism-related pathways along with LPIN2, an inflammasome regulator, as a unique differentially expressed gene (DEG) in infected bronchial epithelial cells from obese subjects. Such findings correlated with altered cytokine and angiotensin-converting enzyme-2 (ACE2) expression during infection of bronchial cells. These findings provide a novel insight on the molecular interplay between obesity and SARS-CoV-2 infection. In conclusion, this study demonstrates the increased SARS-CoV-2 infection of bronchial epithelial cells from obese subjects and highlights the impaired immunity which may explain the increased severity among obese COVID-19 patients.

show abstract

ACE2 polymorphisms impact COVID-19 severity in obese patients

Cited by 8 publications

References 44 publications

Genetic Variants within SARS-CoV-2 Human Receptor Genes May Contribute to Variable Disease Outcomes in Different Ethnicities

Genetic Variants within SARS-CoV-2 Human Receptor Genes May Contribute to Variable Disease Outcomes in Different Ethnicities

Association of specific ACE2 and TMPRSS2 variants with circulatory cytokines of COVID-19 Emirati patients

Lung Epithelial Cells from Obese Patients Have Impaired Control of SARS-CoV-2 Infection

Contact Info

Product

Resources

About