Toll‐like receptor 4 polymorphisms in Saudi population with cardiovascular diseases

Semlali, Abdelhabib; Mutairi, Mikhlid Al; Alanazi, Ibrahim O.; Aljohi, Hasan Awad; Parine, Narasimha Reddy; Alhadheq, Abdullah; Al‐Jafari, Abdulaziz A.; Mobeirek, Abdulelah F. Al; Amri, Abdullah Al; Shaik, Jilani Purusottapatnam; Filali, Fatima‐zohra; Alanazi, Mohammad

doi:10.1002/mgg3.852

Cited by 11 publications

(9 citation statements)

References 61 publications

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“…Multiple molecular studies have been performed on SNPs present in the TLR4 gene, and limited studies have documented different forms of diabetes. In Saudi Arabia, molecular screening for the hepatitis C virus (HCV), glaucoma, leukemia, cancer, and CVD has been undertaken [30][31][32][33][34][35][36][37][38][39]. However, no studies on T2DM have been conducted in the Saudi population, although there is an association between infection, the TLR4 gene, and T2DM.…”

Section: Discussionmentioning

confidence: 99%

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Molecular Effect of Variants in Toll-like Receptor 4 Gene in Saudi Patients with Type 2 Diabetes Mellitus

Alkudmani,

Alshammary,

Ali Khan

2023

Cells

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Single-nucleotide polymorphisms (SNPs) in the Toll-like receptor 4 (TLR4) gene have been documented in type 2 diabetes mellitus (T2DM) and other diseases in the Saudi population. We investigated the relationship between rs11536889, rs4986790, and rs4986791 SNPs in the TLR4 gene and T2DM in the Saudi population; 105 patients with T2DM and 105 healthy controls were analyzed. The TLR4 gene was amplified through PCR, followed by restriction fragment length polymorphism analysis for rs4986791 and Sanger sequencing for rs11536889 and rs4986790 SNPs. The clinical and biochemical characteristics were associated with T2DM (p < 0.05). The rs11536889, rs4986790, and rs4986791 SNPs in control subjects followed the Hardy–Weinberg equilibrium (p > 0.05). Alleles were associated with rs11536889, rs4986791, heterozygous codominant, and dominant models (p < 0.05). However, the rs4986790 SNP was not associated with T2DM (p > 0.05). Logistic regression analysis showed that high-density lipoprotein cholesterol (HDLc) levels were associated with T2DM (p < 0.001). Analysis of variance showed that waist (p = 0.0005) and hip circumferences (p = 0.002) in rs4986790 and rs4986791 SNPs, in SBP (p = 0.001), DBP (p = 0.002), and HDLc levels (p = 0.003), were associated with T2DM subjects. T2DM was also associated with the haplotype (p < 0.001) but not with linkage disequilibrium. The gene–gene interaction was associated with the three SNPs studied in patients with T2DM according to the generalized multifactor dimensionality reduction model (p < 0.0001). Dendrogram and graphical depletion analysis revealed a moderate association in patients with T2DM. The results suggest that rs11536889 and rs4986790 SNPs are genotypically and allelically associated with T2DM in Saudi patients. Future functional studies are recommended to validate the genetic roles of these SNPs in the pathogenesis and progression of diseases.

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Section: Discussionmentioning

confidence: 99%

“…Ten studies have documented the rs4986790 and rs4986791 SNPs' associations with different human diseases in Saudi Arabia [30][31][32][33][34][35][36][37][38][39]. In addition to the rs4986790 and rs4986791 SNPs, other SNPs, such as rs1927906, rs7856729, rs2770150, rs10759931, and rs10759932, were studied.…”

Section: Discussionmentioning

confidence: 99%

Molecular Effect of Variants in Toll-like Receptor 4 Gene in Saudi Patients with Type 2 Diabetes Mellitus

Alkudmani,

Alshammary,

Ali Khan

2023

Cells

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“…In a cohort of mild COVID-19 patients carrying the GG genotype of TLR4 −2604G>A (rs10759931) variant, we identified a significant association between this genotype and the risk for cognitive impairment after SARS-CoV-2 infection. The G allele has already been associated with increased risk for different disorders with immunological basis, including cardiovascular diseases(Semlali et al, 2019), diabetes-associated retinopathy(Singh et al, 2014), cancer(Song et al, 2009), and asthma(Kerkhof et al, 2010). On the other hand, the A allele can affect the binding affinity of the TLR4 promoter to transcription factors, culminating in lower expression of this gene in the allele carriers(Ferronato et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 spike protein induces TLR-4-mediated long-term cognitive dysfunction recapitulating post-COVID syndrome

Fontes-Dantas

Fernandes

Gutman

et al. 2022

Preprint

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COVID-19 pandemic affected the global population in an unprecedented scale, with long-term consequences of SARS CoV-2 infection now emerging as a serious concern. Cognitive dysfunction is often reported in post-COVID patients, but its underlying mechanisms remain unknown. Here we demonstrated that brain exposure to SARS-CoV-2 spike (S) protein through its infusion into the lateral ventricle of adult mice induced late cognitive impairment, hippocampal synapse loss, and microglial engulfment of presynaptic terminals. Additionally, TLR4 blockage prevented Sassociated detrimental effects on memory in mice and TLR4 single nucleotide polymorphism (SNP) rs10759931 was associated with late cognitive outcome in mild COVID-19-recovered patients. Collectively, these findings indicate that S protein directly impacts the brain and identify TLR4 as a key target to prevent cognitive dysfunction. To our knowledge, this is the first animal model that recapitulates postCOVID cognitive impairment, opening new avenues for developing new strategies to prevent or treat the neurological outcomes of COVID-19.

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“…The TLR4 gene ( gene ID 7099 ) is located at chromosome 9q33.1 , and its SNP rs1927914 is located in the 5′ flanking region of the TLR4 gene [ 23 ], while rs11536858 is located in the promotor region. Both may function either by affecting the binding affinity of transcription factors to the regulatory TLR region or by targeting the extracellular domain of TLR4 receptor which controls the receptor binding affinity to its ligands [ 24 ]. On the other side, rs1927911 is located in intron 1 of TLR4 gene and it is not known either is located in a functional site or not.…”

Section: Discussionmentioning

confidence: 99%

TLR4 gene polymorphisms in Egyptian vitiligo patients: insights into emerging association with clinical activity, family history, and response to therapy

Abdel‐Salam

Allam

Zohdy

et al. 2021

Journal of Genetic Engineering and Biotechnology

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Background Vitiligo is a common pigmentary disorder in which autoimmunity has been suggested to play an important role. Toll-like receptor (TLR) family are recognized different molecular structures expressed on immune cells and have been implicated in a number of autoimmune diseases (AIDs) such as vitiligo. The purpose of this study was to investigate the possible association between TLR4 gene polymorphisms: rs11536858, rs1927911, rs1927914 in Egyptian vitiligo patients and their clinical data, their response to therapy. Using PCR-RFLP for TLR4 gene polymorphisms (rs11536858, rs1927911, and rs1927914), both alleles and genotypes were determined after extraction of DNA in a case-control study of 100 vitiligo Egyptian patients and 100 matched age and sex controls. Results The distribution of the protective CT genotype of rs1927914 was higher in the control group. After dividing both patients and controls into 2 age groups (below 18 and above 18 years), no significant associations between the genotypes of the selected TLR4 SNPs and the demographic and clinical data of the vitiligo patients in group 1 (below 18 years) were observed. For group 2 (above 18 years), also no significant associations were found except for the association between the CC genotype of rs1927914 and psychiatric trauma, from one side, and between the CT genotype of rs1927911 and alopecia, from the other side. The association between combined genotypes and the risk of vitiligo showed either higher frequency in patients (risky), or controls (protective), and some equal frequencies (non-significant). The association between haplotypes and risk of vitiligo in patients’ group revealed the highest frequency for the risky ATT and the least frequency for ATC haplotypes. In control group, the protective GCT haplotype showed the highest frequency while the GTC and GCC showed the least frequency. No significant correlations of haplotypes with clinical and demographic data of selected patients’ group were observed apart from that between ACC haplotype and family history of AIDs and between ATT haplotype and remission after phototherapy. Conclusions The significant relationship between TLR4 gene polymorphisms and vitiligo patients charcteristics clarify the role of innate immunity in pathogensis of vitiligo and its effect on the used therapies.

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Toll‐like receptor 4 polymorphisms in Saudi population with cardiovascular diseases

Cited by 11 publications

References 61 publications

Molecular Effect of Variants in Toll-like Receptor 4 Gene in Saudi Patients with Type 2 Diabetes Mellitus

Molecular Effect of Variants in Toll-like Receptor 4 Gene in Saudi Patients with Type 2 Diabetes Mellitus

SARS-CoV-2 spike protein induces TLR-4-mediated long-term cognitive dysfunction recapitulating post-COVID syndrome

TLR4 gene polymorphisms in Egyptian vitiligo patients: insights into emerging association with clinical activity, family history, and response to therapy

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