{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:42:18Z","timestamp":1790847738493,"version":"4.1.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> It is plausible that common disease mechanisms exist in glaucoma pathophysiology. Accordingly, we investigated the genetic association of two previously reported primary open-angle glaucoma (POAG)-related gene polymorphisms, rs2472493 (A &amp;gt; G) in <jats:italic>ABCA1<\/jats:italic> and rs7636836 (C &amp;gt; T) in FNDC3B, in primary angle-closure glaucoma (PACG) and pseudoexfoliation glaucoma (PXG).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> TaqMan genotyping was performed in a total of 442 subjects consisting of 246 healthy controls, 102 PACG patients, and 94 PXG patients. Statistical evaluations were performed to detect allelic and genotype association of the variants with the disease and clinical variables such as intraocular pressure (IOP) and cup\/disc ratio.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Overall, there was no allelic or genotype association of these variants in PACG and PXG. However, rs7636836[T] allele significantly increased the risk of PXG among men (<jats:italic>p<\/jats:italic> = 0.029, odds ratio [OR] = 2.69, 95% confidence interval = 1.11\u20136.51). Similarly, rs2472493 and rs7636836 genotypes also showed significant association with PXG among men in over-dominant model (<jats:italic>p<\/jats:italic> = 0.031, OR = 1.98, 95% CI = 1.06\u20133.71) and co-dominant model (<jats:italic>p<\/jats:italic> = 0.029, OR = 2.69, 95% CI = 1.11\u20136.51), respectively. However, none survived Bonferroni\u2019s correction. Besides, the synergic presence of rs2472493[G] and rs7636836[T] alleles (G-T) was found to significantly increase the risk of PACG (<jats:italic>p<\/jats:italic> = 0.026, OR = 2.85, 95% CI = 1.09\u20137.46). No significant genotype influence was observed on IOP and cup\/disc ratio.<\/jats:p><jats:p><jats:bold>Conclusion<\/jats:bold>: Our results suggest that the polymorphisms rs2472493 in ABCA1 and rs7636836 in FNDC3B genes may be associated with PXG among men, and a G-T allelic combination may confer an increased risk of PACG in the middle-eastern Saudi cohort. Further research in a larger population-based sample is needed to validate these findings.<\/jats:p>","DOI":"10.3389\/fgene.2022.877174","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T11:45:30Z","timestamp":1654083930000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Evaluation of ABCA1 and FNDC3B Gene Polymorphisms Associated With Pseudoexfoliation Glaucoma and Primary Angle-Closure Glaucoma in a Saudi Cohort"],"prefix":"10.3389","volume":"13","author":[{"given":"Altaf A.","family":"Kondkar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahira","family":"Sultan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taif A.","family":"Azad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Essam A.","family":"Osman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal A.","family":"Almobarak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn P.","family":"Lobo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saleh A.","family":"Al-Obeidan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,1]]},"reference":[{"key":"B1","first-page":"2805","article-title":"Analysis of LOXL1 Polymorphisms in a Saudi Arabian Population with Pseudoexfoliation Glaucoma","volume":"16","author":"Abu-Amero","year":"2010","journal-title":"Mol. Vis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/1471-2350-14-84","article-title":"A Catalase Promoter Variant Rs1001179 Is Associated with Visual Acuity but Not with Primary Angle Closure Glaucoma in Saudi Patients","volume":"14","author":"Abu-Amero","year":"2013","journal-title":"BMC Med. Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"180","DOI":"10.3109\/13816810.2013.838276","article-title":"Association of SOD2 Mutation (c.47T > C) with Various Primary Angle Closure Glaucoma Clinical Indices","volume":"36","author":"Abu-Amero","year":"2015","journal-title":"Ophthalmic Genet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.sjopt.2011.09.001","article-title":"The Profile of Glaucoma in a Tertiary Ophthalmic University Center in Riyadh, Saudi Arabia","volume":"25","author":"Al Obeidan","year":"2011","journal-title":"Saudi J. Ophthalmol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"181","DOI":"10.2147\/TACG.S213818","article-title":"Genetic Analysis of ABCA1 Gene of Primary Glaucoma in Jordanian Arab Population","author":"Alkhatib","year":"2019","journal-title":"Tacg"},{"key":"B6","doi-asserted-by":"publisher","first-page":"S12","DOI":"10.1097\/IJG.0000000000000928","article-title":"Genetics of Exfoliation Syndrome","volume":"27","author":"Aung","year":"2018","journal-title":"J. Glaucoma"},{"key":"B7","doi-asserted-by":"publisher","first-page":"e67903","DOI":"10.1371\/journal.pone.0067903","article-title":"Association of Genetic Variants with Primary Angle Closure Glaucoma in Two Different Populations","volume":"8","author":"Awadalla","year":"2013","journal-title":"PLoS One"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1901","DOI":"10.1002\/ijc.29570","article-title":"Integrated Pathway and Epistasis Analysis Reveals Interactive Effect of Genetic Variants atTERF1andAFAP1L2loci on Melanoma Risk","volume":"137","author":"Brossard","year":"2015","journal-title":"Int. J. Cancer"},{"key":"B9","doi-asserted-by":"publisher","first-page":"5439","DOI":"10.1167\/iovs.07-0629","article-title":"Glaucoma-AssociatedCYP1B1Mutations Share Similar Haplotype Backgrounds in POAG and PACG Phenotypes","volume":"48","author":"Chakrabarti","year":"2007","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1136\/bjophthalmol-2014-306102","article-title":"Glaucoma in Asia: Regional Prevalence Variations and Future Projections","volume":"100","author":"Chan","year":"2016","journal-title":"Br. J. Ophthalmol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1038\/ng.3078","article-title":"Common Variants Near ABCA1 and in PMM2 Are Associated with Primary Open-Angle Glaucoma","volume":"46","author":"Chen","year":"2014","journal-title":"Nat. Genet."},{"key":"B12","doi-asserted-by":"publisher","first-page":"2278","DOI":"10.1038\/s41467-018-04555-4","article-title":"A Multiethnic Genome-wide Association Study of Primary Open-Angle Glaucoma Identifies Novel Risk Loci","volume":"9","author":"Choquet","year":"2018","journal-title":"Nat. Commun."},{"key":"B13","doi-asserted-by":"publisher","first-page":"18","DOI":"10.5152\/akd.2013.234","article-title":"Gender Specific Association of ABCA1 Gene R219K Variant in Coronary Disease Risk through Interactions with Serum Triglyceride Elevation in Turkish Adults","volume":"14","author":"Coban","year":"2013","journal-title":"Anadolu Kardiyol. Derg."},{"key":"B14","first-page":"493","article-title":"Two Variants in MYOC and CYP1B1 Genes in a Chinese Family with Primary Angle-Closure Glaucoma","volume":"25","author":"Dai","year":"2008","journal-title":"Zhonghua Yi Xue Yi Chuan Xue Za Zhi"},{"key":"B15","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1167\/iovs.61.6.30","article-title":"Wnt Activation after Inhibition Restores Trabecular Meshwork Cells toward a Normal Phenotype","volume":"61","author":"Dhamodaran","year":"2020","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B16","first-page":"262","article-title":"LOXL1 Gene Polymorphism Candidates for Exfoliation Glaucoma Are Also Associated with a Risk for Primary Open-Angle Glaucoma in a Caucasian Population from Central Russia","volume":"27","author":"Eliseeva","year":"2021","journal-title":"Mol. Vis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1038\/ng.3079","article-title":"Common Variants Near ABCA1, AFAP1 and GMDS Confer Risk of Primary Open-Angle Glaucoma","volume":"46","author":"Gharahkhani","year":"2014","journal-title":"Nat. Genet."},{"key":"B18","doi-asserted-by":"publisher","first-page":"16365","DOI":"10.1038\/s41598-017-16555-3","article-title":"FAD104, a Regulator of Adipogenesis, Is a Novel Suppressor of TGF-\u03b2-Mediated EMT in Cervical Cancer Cells","volume":"7","author":"Goto","year":"2017","journal-title":"Sci. Rep."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1172\/jci44646","article-title":"Molecular Clustering Identifies Complement and Endothelin Induction as Early Events in a Mouse Model of Glaucoma","volume":"121","author":"Howell","year":"2011","journal-title":"J. Clin. Invest."},{"key":"B20","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1167\/iovs.61.5.33","article-title":"ABCA1 Regulates IOP by Modulating Cav1\/eNOS\/NO Signaling Pathway","volume":"61","author":"Hu","year":"2020","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1038\/ng.3087","article-title":"Genome-wide Analysis of Multi-Ancestry Cohorts Identifies New Loci Influencing Intraocular Pressure and Susceptibility to Glaucoma","volume":"46","author":"Hysi","year":"2014","journal-title":"Nat. Genet."},{"key":"B22","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.numecd.2009.05.005","article-title":"The Effects of ABCG5\/G8 Polymorphisms on HDL-Cholesterol Concentrations Depend on ABCA1 Genetic Variants in the Boston Puerto Rican Health Study","volume":"20","author":"Junyent","year":"2010","journal-title":"Nutr. Metabolism Cardiovasc. Dis."},{"key":"B23","doi-asserted-by":"publisher","first-page":"112067212110425","DOI":"10.1177\/11206721211042547","article-title":"Association Analysis of Variants Rs35934224 in TXNRD2 and Rs6478746 in LMX1B in Primary Angle-Closure and Pseudoexfoliation Glaucoma","author":"Kondkar","year":"2021","journal-title":"Eur. J. Ophthalmol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1186\/s12881-020-01076-0","article-title":"Association Analysis of Polymorphisms Rs12997 in ACVR1 and Rs1043784 in BMP6 Genes Involved in Bone Morphogenic Protein Signaling Pathway in Primary Angle-Closure and Pseudoexfoliation Glaucoma Patients of Saudi Origin","volume":"21","author":"Kondkar","year":"2020","journal-title":"BMC Med. Genet."},{"key":"B25","doi-asserted-by":"publisher","first-page":"153","DOI":"10.2147\/OPTH.S155168","article-title":"Elevated Levels of Plasma Tumor Necrosis Factor Alpha in Patients with Pseudoexfoliation Glaucoma","author":"Kondkar","year":"2018","journal-title":"Opth"},{"key":"B26","doi-asserted-by":"publisher","first-page":"347","DOI":"10.3389\/fncel.2018.00347","article-title":"Reduced Annexin A1 Secretion by ABCA1 Causes Retinal Inflammation and Ganglion Cell Apoptosis in a Murine Glaucoma Model","volume":"12","author":"Li","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.1111\/cas.14394","article-title":"FNDC3B 3\u2032\u2010UTR Shortening Escapes from microRNA\u2010mediated Gene Repression and Promotes Nasopharyngeal Carcinoma Progression","volume":"111","author":"Li","year":"2020","journal-title":"Cancer Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"3880","DOI":"10.1093\/hmg\/ddv128","article-title":"A Common Variant Near TGFBR3 Is Associated with Primary Open Angle Glaucoma","volume":"24","author":"Li","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"B29","doi-asserted-by":"publisher","first-page":"6248","DOI":"10.1167\/iovs.15-16741","article-title":"Evaluation of the Association between Common Genetic Variants Near theABCA1Gene and Primary Angle Closure Glaucoma in a Han Chinese Population","volume":"56","author":"Luo","year":"2015","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1038\/ng1537","article-title":"Genome-wide Strategies for Detecting Multiple Loci that Influence Complex Diseases","volume":"37","author":"Marchini","year":"2005","journal-title":"Nat. Genet."},{"key":"B31","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1152\/japplphysiol.00768.2017","article-title":"Cross Talk between Androgen and Wnt Signaling Potentially Contributes to Age-Related Skeletal Muscle Atrophy in Rats","volume":"125","author":"Mumford","year":"20181985","journal-title":"J. Appl. Physiology"},{"key":"B32","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1016\/j.yexcr.2008.12.013","article-title":"Disruption of the Novel Gene Fad104 Causes Rapid Postnatal Death and Attenuation of Cell Proliferation, Adhesion, Spreading and Migration","volume":"315","author":"Nishizuka","year":"2009","journal-title":"Exp. Cell Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1007\/s00439-008-0545-1","article-title":"Network-based Model Weighting to Detect Multiple Loci Influencing Complex Diseases","volume":"124","author":"Pan","year":"2008","journal-title":"Hum. Genet."},{"key":"B34","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1136\/bjophthalmol-2011-301132","article-title":"The Role of Transforming Growth Factor \u03b2 in Glaucoma and the Therapeutic Implications","volume":"97","author":"Prendes","year":"2013","journal-title":"Br. J. Ophthalmol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"21718","DOI":"10.1038\/s41598-021-00961-9","article-title":"Association between the ABCA1 (R219K) Polymorphism and Lipid Profiles: a Meta-Analysis","volume":"11","author":"Shi","year":"2021","journal-title":"Sci. Rep."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1093\/hmg\/ddy053","article-title":"Genome-wide Association Study Identifies Seven Novel Susceptibility Loci for Primary Open-Angle Glaucoma","volume":"27","author":"Shiga","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"B37","first-page":"64","article-title":"Expression of Androgen Receptor in Mouse Eye Tissues","volume":"41","author":"Tachibana","year":"2000","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.febslet.2004.09.062","article-title":"The Novel Gene Fad104, Containing a Fibronectin Type III Domain, Has a Significant Role in Adipogenesis","volume":"577","author":"Tominaga","year":"2004","journal-title":"FEBS Lett."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/IIO.0000000000000047","article-title":"Genomic and Proteomic Pathophysiology of Pseudoexfoliation Glaucoma","volume":"54","author":"Vazquez","year":"2014","journal-title":"Int. Ophthalmol. Clin."},{"key":"B40","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1002\/biof.1187","article-title":"ABCA1 and Nascent HDL Biogenesis","volume":"40","author":"Wang","year":"2014","journal-title":"Biofactors"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1454","DOI":"10.1167\/iovs.17-21964","article-title":"The Role of Wnt\/\u03b2-Catenin Signaling and K-Cadherin in the Regulation of Intraocular Pressure","volume":"59","author":"Webber","year":"2018","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1901","DOI":"10.1001\/jama.2014.3192","article-title":"The Pathophysiology and Treatment of Glaucoma","volume":"311","author":"Weinreb","year":"2014","journal-title":"JAMA"},{"key":"B43","doi-asserted-by":"publisher","first-page":"2795","DOI":"10.1167\/iovs.13-13323","article-title":"Activation of Liver X Receptor Alleviates Ocular Inflammation in Experimental Autoimmune Uveitis","volume":"55","author":"Yang","year":"2014","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1186\/1471-2164-14-569","article-title":"Combined Genotype and Haplotype Tests for Region-Based Association Studies","volume":"14","author":"Zakharov","year":"2013","journal-title":"BMC Genomics"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2013\/202905","article-title":"Integrins in Trabecular Meshwork and Optic Nerve Head: Possible Association with the Pathogenesis of Glaucoma","volume":"2013","author":"Zhong","year":"2013","journal-title":"BioMed Res. Int."},{"key":"B46","doi-asserted-by":"publisher","first-page":"55","DOI":"10.3390\/genes12010055","article-title":"Molecular Genetics of Glaucoma: Subtype and Ethnicity Considerations","volume":"12","author":"Zukerman","year":"2021","journal-title":"Genes"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.877174\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T11:45:35Z","timestamp":1654083935000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.877174\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,1]]},"references-count":46,"alternative-id":["10.3389\/fgene.2022.877174"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.877174","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,1]]},"article-number":"877174"}}