Evaluation of ABCA1 and FNDC3B Gene Polymorphisms Associated With Pseudoexfoliation Glaucoma and Primary Angle-Closure Glaucoma in a Saudi Cohort

Kondkar, Altaf A.; Sultan, Tahira; Azad, Taif A.; Osman, Essam; Almobarak, Faisal A.; Lobo, Glenn P.; Al‐Obeidan, Saleh A.

doi:10.3389/fgene.2022.877174

Cited by 5 publications

(3 citation statements)

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“…By contrast, another large multi-ethnic meta-analysis reported a negative association ( 138 ). Studies in Brazilian, Afroamerican, Chinese, and Arab populations failed to detect any association between this Abca1 polymorphism and different types of glaucoma ( 132 , 133 , 136 , 140 , 141 ). Interestingly, it was recently shown that this rs2472493 genetic variant attenuates Abca1 expression in a model of cultured cells using a luciferase reporter gene under the control of a human Abca1 promoter harboring the POAG risk allele [G] ( 66 ).…”

Section: Cholesterol Oxysterols and Glaucomamentioning

confidence: 91%

Cholesterol and oxysterols in retinal neuron-glia interactions: relevance for glaucoma

Masson,

Serrano,

Leger-Charnay

et al. 2024

Front. Ophthalmol.

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Cholesterol is an essential component of cellular membranes, crucial for maintaining their structural and functional integrity. It is especially important for nervous tissues, including the retina, which rely on high amounts of plasma membranes for the transmission of the nervous signal. While cholesterol is by far the most abundant sterol, the retina also contains cholesterol precursors and metabolites, especially oxysterols, which are bioactive molecules. Cholesterol lack or excess is deleterious and some oxysterols are known for their effect on neuron survival. Cholesterol homeostasis must therefore be maintained. Retinal glial cells, especially Müller cells, the principal glial cells of the vertebrate retina, provide mechanical, nutritional, and metabolic support for the neighboring neurons. Several pieces of evidence indicate that Müller cells are major actors of cholesterol homeostasis in the retina, as it is known for other glial cells in the brain. This process is based on a close cooperation with neurons, and sterols can be signaling molecules participating in glia-neuron interactions. While some implication of cholesterol in age-related macular degeneration is now recognized, based on epidemiological and laboratory data, evidence for its role in glaucoma is still scarce. The association between cholesterolemia and glaucoma is controversial, but experimental data suggest that sterols could take part in the pathological processes. It has been demonstrated that Müller glial cells are implicated in the development of glaucoma through an ambivalent reactive retinal gliosis process. The early steps contribute to maintaining retinal homeostasis and favor the survival of ganglion cells, which are targeted during glaucoma. If gliosis persists, dysregulation of the neuroprotective functions, cytotoxic effects of gliotic Müller cells and disruption of glia-neuron interactions lead to an acceleration of ganglion cell death. Sterols could play a role in the glial cell response to glaucomatous injury. This represents an understudied but attractive topic to better understand glaucoma and conceive novel preventive or curative strategies. The present review describes the current knowledge on i) sterol metabolism in retinal glial cells, ii) the potential role of cholesterol in glaucoma, and iii) the possible relationships between cholesterol and oxysterols, glial cells and glaucoma. Focus is put on glia-neuron interactions.

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Section: Cholesterol Oxysterols and Glaucomamentioning

confidence: 91%

Cholesterol and oxysterols in retinal neuron-glia interactions: relevance for glaucoma

Masson,

Serrano,

Leger-Charnay

et al. 2024

Front. Ophthalmol.

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“…DNA extracted from EDTA blood were genotyped for the rs2472493 (A > G), rs7636836 (C > T), and rs61275591 (G > A) polymorphisms using commercially available TaqMan ® assays, C__16235609_10, C_189412462_10, and C__88653935_10 (catalog number: 4351379; Applied Biosystems Inc., Foster City, CA, USA) on ABI-7500 real-time PCR (Applied Biosystems) as recommended by the manufacturer and described previously [ 21 ].…”

Section: Methodsmentioning

confidence: 99%

Lack of Association of Polymorphism Located Upstream of ABCA1 (rs2472493), in FNDC3B (rs7636836), and Near ANKRD55–MAP3K1 Genes (rs61275591) in Primary Open-Angle Glaucoma Patients of Saudi Origin

Kondkar

Sultan

Azad

et al. 2023

Genes

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Polymorphisms rs2472493 near ABCA1, rs7636836 in FNDC3B, and rs61275591 near the ANKRD55–MAP3K1 genes were previously reported to exhibit genome-wide significance in primary open-angle glaucoma (POAG). Since these polymorphisms have not been investigated in the Arab population of Saudi Arabia, we examined their association with POAG in a Saudi cohort. Genotyping was performed in 152 POAG cases and 246 controls using Taqman real-time assays and their associations with POAG and clinical markers, such as intraocular pressure, cup/disc ratio, and the number of antiglaucoma medications, were tested by statistical methods. There was no association observed between POAG and the minor allele frequencies of rs2472493[G], rs7636836[T], or rs61275591[A]. None of the genetic models such as co-dominant, dominant, recessive, over-dominant, and log-additive demonstrated any genotype link. The Rs2472493 genotype showed a modest association (p = 0.044) with the number of antiglaucoma medications in the POAG group, but no significant genotype effect on post hoc analysis. In addition, a G-T allelic haplotype of rs2472493 (ABCA1) and rs7636836 (FNDC3B) did show an over two-fold increased risk of POAG (odds ratio = 2.18), albeit non-significantly (p = 0.092). Similarly, no other allelic haplotype of the three variants showed any significant association with POAG. Our study did not replicate the genetic association of rs2472493 (ABCA1), rs763683 (FNDC3B), and rs61275591 (ANKRD55–MAP3K1) in POAG and related clinical phenotypes, suggesting that these polymorphisms are not associated with POAG in a Saudi cohort of Arab ethnicity. However, large population-based multicenter studies are needed to validate these results.

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“…We conducted a retrospective and exploratory case-control study, sanctioned by the Institutional Review Board Ethics Committee at the College of Medicine of King Saud University as per the principles of the Declaration of Helsinki guidelines for human research. Participants were recruited at King Abdulaziz University Hospital in Riyadh, Saudi Arabia, as described elsewhere [58].…”

Section: Study Design Ethics Approval and Participant Characteristicsmentioning

confidence: 99%

APOE ε2-Carriers Are Associated with an Increased Risk of Primary Angle-Closure Glaucoma in Patients of Saudi Origin

Kondkar,

Azad,

Sultan

et al. 2024

IJMS

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This study investigated the association between apolipoprotein E (APOE) gene polymorphisms (rs429358 and rs7412) and primary angle-closure glaucoma (PACG) and pseudoexfoliation glaucoma (PXG) in a Saudi cohort. Genotyping of 437 DNA samples (251 controls, 92 PACG, 94 PXG) was conducted using PCR-based Sanger sequencing. The results showed no significant differences in the allele and genotype frequencies of rs429358 and rs7412 between the PACG/PXG cases and controls. Haplotype analysis revealed ε3 as predominant, followed by ε4 and ε2 alleles, with no significant variance in PACG/PXG. However, APOE genotype analysis indicated a significant association between ε2-carriers and PACG (odds ratio = 4.82, 95% CI 1.52–15.26, p = 0.007), whereas no notable association was observed with PXG. Logistic regression confirmed ε2-carriers as a significant predictor for PACG (p = 0.008), while age emerged as significant for PXG (p < 0.001). These findings suggest a potential role of ε2-carriers in PACG risk within the Saudi cohort. Further validation and larger-scale investigations are essential to elucidate the precise role of APOE in PACG pathogenesis and progression.

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Evaluation of ABCA1 and FNDC3B Gene Polymorphisms Associated With Pseudoexfoliation Glaucoma and Primary Angle-Closure Glaucoma in a Saudi Cohort

Cited by 5 publications

References 42 publications

Cholesterol and oxysterols in retinal neuron-glia interactions: relevance for glaucoma

Cholesterol and oxysterols in retinal neuron-glia interactions: relevance for glaucoma

Lack of Association of Polymorphism Located Upstream of ABCA1 (rs2472493), in FNDC3B (rs7636836), and Near ANKRD55–MAP3K1 Genes (rs61275591) in Primary Open-Angle Glaucoma Patients of Saudi Origin

APOE ε2-Carriers Are Associated with an Increased Risk of Primary Angle-Closure Glaucoma in Patients of Saudi Origin

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