Analysis of toll-like receptor rs4986790 polymorphism in Saudi patients with primary open angle glaucoma

Abu-Amero, Khaled K.; Kondkar, Altaf A.; Mousa, Ahmed; Azad, Taif A.; Sultan, Tahira; Osman, Essam; Al-Obeidan, Saleh A.

doi:10.3109/13816810.2016.1151900

Cited by 11 publications

(10 citation statements)

References 27 publications

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“…However, these results may be population specific as another report of a NTG Korean population demonstrated no statistical significance difference between the NTG patients and controls for www.nature.com/scientificreports www.nature.com/scientificreports/ SNPs (rs10759930, rs1927914, rs1927911, rs12377632, rs2149356, rs11536889, rs7037117, and rs7045953) in the TLR4 gene 55 . And, Abu-Amero and colleagues evaluated the SNP at s4986790 in the TLR4 gene of Saudi POAG patients, and found no statistical difference compared to controls 56 . Importantly, the role of TLR4 in fibrogenesis has also been identified and confirmed by specific SNP alleles in TLR4 being associated with a delayed progression of fibrosis in liver disease and conferring an overall protective effect 57,58 .…”

Section: Discussionmentioning

confidence: 99%

Fibronectin extra domain A (FN-EDA) elevates intraocular pressure through Toll-like receptor 4 signaling

Roberts

Mavlyutov

Perlmutter

et al. 2020

Sci Rep

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Elevated intraocular pressure (IOP) is a major risk factor for the development and progression of primary open angle glaucoma and is due to trabecular meshwork (TM) damage, which leads to impaired aqueous humor outflow. Here, we explore a novel molecular mechanism involved in glaucomatous TM damage. We investigated the role of an endogenous Toll-like receptor 4 (TLR4) ligand, fibronectin-EDA (FN-EDA), in TGFβ2-induced ocular hypertension in mice. We utilized transgenic mouse strains that either constitutively express only FN containing the EDA isoform or contain an EDA-null allele and express only FN lacking EDA, with or without a mutation in Tlr4, in our inducible mouse model of ocular hypertension by injection of Ad5.TGFβ2. IOP was measured over time and eyes accessed by immunohistochemistry for total FN and FN-EDA expression. Constitutively active EDA caused elevated IOP starting at 14 weeks of age. Ad5.TGFβ2 induced ocular hypertension in wildtype C57BL/6J mice and further amplified the IOP in constitutively active EDA mice. TLR4 null and EDA null mice blocked Ad5.TGFβ-induced ocular hypertension. Total FN and FN-EDA isoform expression increased in response to Ad5.TGFβ2. These data suggest that both TLR4 and FN-EDA contribute to TGFβ2 induced ocular hypertension.

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Section: Discussionmentioning

confidence: 99%

Fibronectin extra domain A (FN-EDA) elevates intraocular pressure through Toll-like receptor 4 signaling

Roberts

Mavlyutov

Perlmutter

et al. 2020

Sci Rep

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“…This might cause a dysfunction of the TLR4 molecule and interfere with the host immune system. Currently, two research teams from Saudi Arabia [18, 19] and Mexico [21] focused on rs4986790 and rs4986791 polymorphisms, only to yield inconsistent results. Confronting ethnic disparities, meta-analyses were not performed in these two SNPs.…”

Section: Discussionmentioning

confidence: 99%

Associations between TLR4 Polymorphisms and Open Angle Glaucoma: A Meta-Analysis

Lin

Huang

Sun

et al. 2019

BioMed Research International

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Background. Previous studies exploring the association between toll-like receptor 4 (TLR4) polymorphisms and open angle glaucoma (OAG) presented inconsistent results. We aimed to investigate the association between TLR4 polymorphisms and OAG. Methods. A systematic literature search was conducted in PubMed, EMBASE, ISI Web of Knowledge, and the Cochrane Library up to 31 December 2018. Odds ratio (OR) and 95% confidence interval (95%CI) were calculated, followed by stratification analyses according to ethnicity and glaucoma subtype. Results. TLR4 rs7037117 polymorphism had significant associations with increased risk of OAG in allelic model (OR=1.25; 95%CI: 1.09-1.44; P=0.002) and recessive model (OR=1.49; 95%CI: 1.08-2.04; P=0.01). With regard to rs10759930, rs12377632, and rs2149356, the results showed significant increased risks in all genetic models (all P<0.05), whereas, for rs1927914, rs11536889, and rs7045953, no significant associations were identified in any genetic model (all P>0.05). Furthermore, the association of rs1927911 with OAG risk was found to be significant in recessive model (OR=1.34; 95%CI: 1.06-1.71; P=0.02). As for rs4986790 and rs4986791, meta-analyses were not performed due to the limited number of studies and the ethnic differences. Subgroup analysis indicated that the above polymorphisms with significant differences might increase the susceptibility in POAG patients. As for the ethnicity, rs7037117, rs10759930, and rs1927911 might increase the risk in Asians, while rs12377632 and rs2149356 might increase the risk in Asians and Mexicans. Conclusion. The meta-analysis highlighted that certain mutations of some TLR4 polymorphisms might increase the susceptibility of OAG. However, TLR4 polymorphisms are still far from being candidate genetic biomarkers for OAG. Additional researches involving larger scale epidemiological studies are warranted to validate our results.

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“…The VIC ® and 6-carboxy-fluorescein (FAM) fluorescence levels of the PCR products were measured at 60 °C for 1 min. A fluorescence analysis was performed using automated 2-color allele discrimination software to identify the DICER1 and DROSHA genotypes on a 2-dimensional graph [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

Polymorphism rs3742330 in microRNA Biogenesis Gene DICER1 Is Associated with Pseudoexfoliation Glaucoma in Saudi Cohort

Kondkar

Azad

Sultan

et al. 2022

Genes

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We investigated the association between DICER1 (rs3742330) and DROSHA (rs10719) polymorphisms and pseudoexfoliation glaucoma (PXG) and related clinical phenotypes in a Saudi cohort. In a retrospective case-control study, TaqMan real-time, PCR-based genotyping was performed in 340 participants with 246 controls and 94 PXG cases. The minor (G) allele frequency of rs3742330 in PXG (0.03) was significantly different from that in the controls (0.08) and protective against PXG (odds ratio (OR) = 0.38, 95% confidence interval (CI) = 0.16–0.92), p = 0.017). Similarly, the rs3742330 genotypes showed a significant protective association with PXG in dominant (p = 0.019, OR = 0.38, 95% CI = 0.15–0.92), over-dominant (p = 0.024, OR = 0.39, 95% CI = 0.16–0.95), and log-additive models (p = 0.017, OR = 0.38, 95% CI = 0.16–0.92). However, none remained significant after an adjustment for age, sex, and multiple testing. Rs10719 in DROSHA did not show any significant allelic or genotype association with PXG. However, a protective effect of the GA haplotype in DICER1 and DROSHA and PXG (p = 0.034) was observed. Both polymorphisms showed no significant effect on intraocular pressure and the cup–disk ratio. In conclusion, we report a significant genetic association between variant rs3742330 in DICER1, a gene involved in miRNA biogenesis, and PXG. Further investigation in a larger group of patients of different ethnicities and functional studies are warranted to replicate and validate its potential role in PXG.

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Analysis of toll-like receptor rs4986790 polymorphism in Saudi patients with primary open angle glaucoma

Cited by 11 publications

References 27 publications

Fibronectin extra domain A (FN-EDA) elevates intraocular pressure through Toll-like receptor 4 signaling

Fibronectin extra domain A (FN-EDA) elevates intraocular pressure through Toll-like receptor 4 signaling

Associations between TLR4 Polymorphisms and Open Angle Glaucoma: A Meta-Analysis

Polymorphism rs3742330 in microRNA Biogenesis Gene DICER1 Is Associated with Pseudoexfoliation Glaucoma in Saudi Cohort

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