Evidence map›Paper›PMID 41761307›Full record

ArticleHuman genomics2026

Genetic variations in AAK1 and ADAM17 associated with circulatory cytokines changes influence COVID-19 susceptibility and severity.

Amal Bouzid, Noha M Elemam, Habiba Alsafar, Thenmozhi Venkatachalam, Leen Eldoahji, Nour Halabi, Mohamed A Saleh, Iman M Talaat, Jalal Taneera, Nabil Sulaiman and 4 more

Abstract read
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Article in Human genomics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

14 authors.

Amal Bouzid *Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates.
Noha M Elemam *Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates.
Habiba AlsafarCenter for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates. habiba.alsafar@ku.ac.ae.
Thenmozhi VenkatachalamResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates.
Leen EldoahjiResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates.
Nour HalabiInstitut Imagine, Paris, France.
Mohamed A SalehResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates.
Iman M TalaatResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates.
Jalal TaneeraResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates.
Nabil SulaimanResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates.
Azzam A MaghazachiResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates.
Qutayba HamidResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates.
Rifat HamoudiResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates.
Maha Saber-AyadResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates. msaber@sharjah.ac.ae.

Funding

University of Sharjah CoV19-0304
6 · The paper itself

Abstract

backgroundThe interplay between genetic factors and COVID-19 susceptibility and severity underscores the critical roles of genetic variations in the responses to the virus. Specifically, genetic variations in genes such as AAK1 and ADAM17 may influence the molecular pathways that determine how the virus enters cells and how the immune system responds, thereby affecting disease outcomes. Identifying these potential genetic variants clarifies individual responses to infectious diseases and helps aid in developing effective targeted therapeutic strategies.

methodsWe performed targeted next-generation sequencing focusing on specific single-nucleotide variants (SNVs) in AAK1, ADAM17, and CD209 genes, which are implicated in the entry of SARS-CoV-2 into host cells. The study was conducted in a Middle Eastern cohort, comprising 96 COVID-19 patients with varying disease severities and 69 healthy controls. The correlation between the prevalence of the investigated genetic variants and the serum level of inflammatory cytokines within the studied cohort was also evaluated.

resultsOur analysis revealed statistically significant differences in genetic variants between COVID-19 patients and healthy controls. Notably, a 5'UTR variant, rs12692386: chr2:9695906, A > G, in the ADAM17 gene showed a significant association (p = 0.039). Additionally, two variants in the AAK1 gene, an intronic variant chr2:69732672, C > A (p = 0.029) and a missense variant rs1275698668: chr2:69747984, G > C (p = 0.017), were identified, suggesting their potential role in influencing disease susceptibility and severity. The gender-stratified analysis between the two groups showed a significant difference in the AAK1-SNV-rs1275698668 (p = 0.027) in female susceptibility, suggesting a protective effect against SARS-CoV-2 infection. The AAK1-SNV-rs1275698668 showed a significant difference between the three severity groups (p = 0.045). Prediction in-silico tools suggest that 2:g.69747984G > C and 2:g.9,695,906 A > G have potential functional/regulatory impacts on the ADAM17 and AAK1 genes, respectively. Moreover, different correlation patterns between the identified genetic variants and inflammatory cytokine levels (including CD40 ligand, IL-1b, GM-CSF, and IL-4) were observed in COVID-19 patients.

conclusionsOur findings suggest potential genetic biomarkers in AAK1 and ADAM17 genes that could affect the disease severity and circulating cytokine levels in COVID-19 patients.

Indexed as

ADAM17 ProteinCOVID-19CytokinesGenetic Predisposition to DiseaseAdultCase-Control StudiesFemaleHumansMaleMiddle AgedPolymorphism, Single NucleotideSARS-CoV-2Severity of Illness IndexADAM17 ProteinADAM17 protein, humanCytokinesAAK1ADAM17COVID-19CytokinesGenetic variantsSARS-CoV-2

Identifiers

PMID41761307
PMCPMC13049976

What Socratic holds

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LicenceCC BY-NC-ND
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.