Impact of Toll-Like Receptor 2 and 9 Gene Polymorphisms on COVID-19: Susceptibility, Severity, and Thrombosis

Alhabibi, Alshaymaa M; Hassan, Asmaa S.; Elbaky, Nashwa Mohamed Abd; Eid, Hoda A.; Khalifa, Mohie Aldeen Abd Alzaher; Wahab, Maisa A Abdel; Althoqapy, Azza Ali; Abdou, Aml E; Zakaria, Doaa Mohammed; Nassef, Eman Mostafa; Kasim, Sammar Ahmed; Saleh, Ola I; Elsheikh, Asmaa Abdelghany; Lotfy, Mahmoud; Sayed, Alaa El‐Din H.

doi:10.2147/jir.s394927

Cited by 8 publications

(8 citation statements)

References 47 publications

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“…In the presence of TLR2 -rs5743708 and/or TLR4 -rs4986791 polymorphisms, reduced binding affinity for E and S proteins, respectively may explain the inadequate immune response against SARS-CoV-2 that fails to control infection, worsening the disease outcome. Therefore, our data further support the results of two previous studies from Egypt, where a positive correlation between the aforementioned polymorphisms and COVID-19 severity was observed [ 38 , 39 ], suggesting that both SNPs could be used as molecular predictors of COVID-19 prognosis and outcome.…”

Section: Discussionsupporting

confidence: 91%

Innate Immune Gene Polymorphisms and COVID-19 Prognosis

Bakaros,

Voulgaridi,

Paliatsa

et al. 2023

Viruses

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COVID-19 is characterized by a heterogeneous clinical presentation and prognosis. Risk factors contributing to the development of severe disease include old age and the presence of comorbidities. However, the genetic background of the host has also been recognized as an important determinant of disease prognosis. Considering the pivotal role of innate immunity in the control of SARS-CoV-2 infection, we analyzed the possible contribution of several innate immune gene polymorphisms (including TLR2-rs5743708, TLR4-rs4986790, TLR4-rs4986791, CD14-rs2569190, CARD8-rs1834481, IL18-rs2043211, and CD40-rs1883832) in disease severity and prognosis. A total of 249 individuals were enrolled and further divided into five (5) groups, according to the clinical progression scale provided by the World Health Organization (WHO) (asymptomatic, mild, moderate, severe, and critical). We identified that elderly patients with obesity and/or diabetes mellitus were more susceptible to developing pneumonia and respiratory distress syndrome after SARS-CoV-2 infection, while the IL18-rs1834481 polymorphism was an independent risk factor for developing pneumonia. Moreover, individuals carrying either the TLR2-rs5743708 or the TLR4-rs4986791 polymorphisms exhibited a 3.6- and 2.5-fold increased probability for developing pneumonia and a more severe disease, respectively. Our data support the notion that the host’s genetic background can significantly affect COVID-19 clinical phenotype, also suggesting that the IL18-rs1834481, TLR2-rs5743708, and TLR4-rs4986791 polymorphisms may be used as molecular predictors of COVID-19 clinical phenotype.

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Section: Discussionsupporting

confidence: 91%

Innate Immune Gene Polymorphisms and COVID-19 Prognosis

Bakaros,

Voulgaridi,

Paliatsa

et al. 2023

Viruses

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“…Despite the small sample size in our current investigation, it is noteworthy that analogous studies have previously performed association analyses in similarly small sample sizes to gain initial insights before undertaking extensive validation endeavors in larger populations [46][47][48]. In line with these previous reports, our study conducted a preliminary analysis within a limited cohort, revealing no association between TLR7 (rs864058) polymorphism and susceptibility to COVID-19.…”

Section: Discussionsupporting

confidence: 50%

No Association between SARS-CoV-2 Infection and the Polymorphism of the Toll-like Receptor 7 (TLR7) Gene in Female Population

Zayed,

Kim,

Lee

et al. 2023

Diagnostics

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Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-stranded RNA virus. Toll-like receptor 7 (TLR7) recognizes single-stranded RNA viruses. The TLR7 gene plays a critical role in the human innate and adaptive immune response to SARS-CoV-2 infections. Genetic factors probably affect SARS-CoV-2 infection susceptibility. In the current study, our aim was to search for genetic variations associated with COVID-19 patients in the TLR7 gene of a Korean population. We designed five gene-specific primers to cover the coding region of the human TLR7 gene. Using amplicon sequencing, we screened the genetic polymorphisms in the coding region of the TLR7 gene in COVID-19 patients and healthy controls. The genotype frequencies, allele frequencies, and Hardy–Weinberg equilibrium (HWE) were examined. We identified a low-frequency synonymous single nucleotide polymorphism (SNP) (rs864058) in the coding region of the TLR7 gene. There were no significant differences in the genotype or allele frequencies of the TLR7 rs864058 polymorphism between COVID-19 female patients and healthy controls (p = 1.0). In conclusion, TLR7 (rs864058) polymorphism is low frequency in Korean populations and is not associated with SARS-CoV-2 infection.

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“…SNPs and mutation in the TLRs may lead problem in signal transduction, and this problem may lead recurrence of viral diseases (20). Since TLR7 is required for type-I interferone (IFN) response, the role of TLR7 SNPs in the COVID-19 pathogenesis may be associated to increased type-I IFN response (21). TLR7 rs179008 polymorphism was linked with increased susceptibility to COVID-19 infection (22).…”

Section: Discussionmentioning

confidence: 99%

Relationship of Toll-Like Receptor 7, 9, and 10 Polymorphisms and the Severity of Coronavirus Disease 2019

Bayyurt,

Baltacı,

Şahin

et al. 2024

Jpn J Infect Dis

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COVID-19 is an pandemic that is still affecting today and has caused many deaths. Toll-like receptor (TLR) have an important role in the binding of disease agents to host cell, disease susceptibility and severity, host disease resistance, In this study, we investigated frequencies of TLR7 (C.4-151 A/G), TLR9 (T-1486C and G2848A), and TLR10 (720A/C and 992T/A) single nucleotide polymorphisms (SNPs) in 150 cases with COVID-19 and 171 control samples. We also observed whether TLR7, 9, and 10 were related with the COVID-19 disease severity. Furthermore, we analyzed the association between COVID-19 and some clinical parameters. Polymerase chain reaction (PCR) based on restriction fragment length polymorphism (RFLP) was performed for TLR7, 9 and 10 SNPs. TLR7 C.4-151 A/G G allele and GG genotype; TLR9 T-1486C C allele and TC, CC genotypes; and TLR10 720A/C C allele; TLR10 992T/A A allele and AA genotype frequencies were statistic significant in cases compared with controls (P<0.05*). In addition, there was a statistic significant difference in the distribution of TLR7, 9, and 10 allele and genotype frequencies between severity groups (P<0.05*). Our findings suggest that TLR7, 9, and 10 polymorphisms may be crucial on clinical course or susceptibility of the infection.

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Impact of Toll-Like Receptor 2 and 9 Gene Polymorphisms on COVID-19: Susceptibility, Severity, and Thrombosis

Cited by 8 publications

References 47 publications

Innate Immune Gene Polymorphisms and COVID-19 Prognosis

Innate Immune Gene Polymorphisms and COVID-19 Prognosis

No Association between SARS-CoV-2 Infection and the Polymorphism of the Toll-like Receptor 7 (TLR7) Gene in Female Population

Relationship of Toll-Like Receptor 7, 9, and 10 Polymorphisms and the Severity of Coronavirus Disease 2019

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