{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T14:49:52Z","timestamp":1777042192731,"version":"3.51.4"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T00:00:00Z","timestamp":1678665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Saud University through the Vice Deanship of Scientific Research Chair and Glaucoma Research Chair in Ophthalmology","award":["GRC-2023"],"award-info":[{"award-number":["GRC-2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Polymorphisms rs2472493 near ABCA1, rs7636836 in FNDC3B, and rs61275591 near the ANKRD55\u2013MAP3K1 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\u2013MAP3K1) 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.<\/jats:p>","DOI":"10.3390\/genes14030704","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T06:52:13Z","timestamp":1678690333000},"page":"704","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Lack of Association of Polymorphism Located Upstream of ABCA1 (rs2472493), in FNDC3B (rs7636836), and Near ANKRD55\u2013MAP3K1 Genes (rs61275591) in Primary Open-Angle Glaucoma Patients of Saudi Origin"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5516-6951","authenticated-orcid":false,"given":"Altaf A.","family":"Kondkar","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia"},{"name":"Glaucoma Research Chair in Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia"},{"name":"King Saud University Medical City, King Saud University, Riyadh 11411, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tahira","family":"Sultan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taif A.","family":"Azad","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Essam A.","family":"Osman","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3504-2828","authenticated-orcid":false,"given":"Faisal A.","family":"Almobarak","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia"},{"name":"Glaucoma Research Chair in Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenn P.","family":"Lobo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55347, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0573-4017","authenticated-orcid":false,"given":"Saleh A.","family":"Al-Obeidan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia"},{"name":"Glaucoma Research Chair in Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.sjopt.2019.02.006","article-title":"The prevalence and determinants of glaucoma among 40 years and older saudi residents in the riyadh governorate (except the capital)\u2014A community based survey","volume":"33","author":"Khandekar","year":"2019","journal-title":"Saudi J. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1001\/jama.2014.3192","article-title":"The pathophysiology and treatment of glaucoma: A review","volume":"311","author":"Weinreb","year":"2014","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.optom.2016.02.003","article-title":"Glaucoma history and risk factors","volume":"10","author":"McMonnies","year":"2017","journal-title":"J. Optom."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"107795","DOI":"10.1016\/j.exer.2019.107795","article-title":"Update on the genetics of primary open-angle glaucoma","volume":"188","author":"Youngblood","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1038\/s41467-020-20851-4","article-title":"Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries","volume":"12","author":"Gharahkhani","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1038\/ng.3087","article-title":"Genome-wide analysis of multiethnic cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma","volume":"46","author":"Hysi","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","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":"ref_8","doi-asserted-by":"crossref","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":"ref_9","doi-asserted-by":"crossref","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":"ref_10","doi-asserted-by":"crossref","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":"ref_11","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.nbd.2013.01.018","article-title":"Abca1 influences neuroinflammation and neuronal death","volume":"54","author":"Karasinska","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s11427-021-2126-2","article-title":"Cholesterol homeostasis regulated by abca1 is critical for retinal ganglion cell survival","volume":"66","author":"Yang","year":"2023","journal-title":"Sci. China Life Sci."},{"key":"ref_13","doi-asserted-by":"crossref","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":"ref_14","doi-asserted-by":"crossref","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":"ref_15","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.4161\/cc.20121","article-title":"Activation of multiple cancer pathways and tumor maintenance function of the 3q amplified oncogene fndc3b","volume":"11","author":"Cai","year":"2012","journal-title":"Cell. Cycle"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zukerman, R., Harris, A., Verticchio Vercellin, A., Siesky, B., Pasquale, L.R., and Ciulla, T.A. (2021). Molecular genetics of glaucoma: Subtype and ethnicity considerations. Genes, 12.","DOI":"10.3390\/genes12081135"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"181","DOI":"10.2147\/TACG.S213818","article-title":"Genetic analysis of abca1 gene of primary glaucoma in jordanian arab population","volume":"12","author":"Alkhatib","year":"2019","journal-title":"Appl. Clin. Genet."},{"key":"ref_18","first-page":"1283","article-title":"Study of myoc gene mutation in poag patients in zahedan, iran","volume":"63","author":"Rasouli","year":"2017","journal-title":"Clin. Lab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"28886","DOI":"10.3390\/ijms161226135","article-title":"An updated review on the genetics of primary open angle glaucoma","volume":"16","author":"Kondkar","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"690780","DOI":"10.3389\/fgene.2021.690780","article-title":"Lack of association between polymorphisms in txnrd2 and lmx1b and primary open-angle glaucoma in a saudi cohort","volume":"12","author":"Kondkar","year":"2021","journal-title":"Front. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"877174","DOI":"10.3389\/fgene.2022.877174","article-title":"Evaluation of abca1 and fndc3b gene polymorphisms associated with pseudoexfoliation glaucoma and primary angle-closure glaucoma in a saudi cohort","volume":"13","author":"Kondkar","year":"2022","journal-title":"Front. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zukerman, R., Harris, A., Oddone, F., Siesky, B., Verticchio Vercellin, A., and Ciulla, T.A. (2021). Glaucoma heritability: Molecular mechanisms of disease. Genes, 12.","DOI":"10.3390\/genes12081135"},{"key":"ref_23","doi-asserted-by":"crossref","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":"ref_24","doi-asserted-by":"crossref","first-page":"6248","DOI":"10.1167\/iovs.15-16741","article-title":"Evaluation of the association between common genetic variants near the abca1 gene and primary angle closure glaucoma in a han chinese population","volume":"56","author":"Luo","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_25","first-page":"1","article-title":"Association of abca1 (rs2472493) and gas7 (rs9913911) gene variants with primary open-angle glaucoma in a brazilian population","volume":"28","author":"Araki","year":"2022","journal-title":"Mol. Vis."},{"key":"ref_26","doi-asserted-by":"crossref","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":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","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":"ref_28","doi-asserted-by":"crossref","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":"ref_29","doi-asserted-by":"crossref","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":"ref_30","doi-asserted-by":"crossref","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":"ref_31","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1111\/cas.14394","article-title":"Fndc3b 3\u2019-utr shortening escapes from microrna-mediated gene repression and promotes nasopharyngeal carcinoma progression","volume":"111","author":"Li","year":"2020","journal-title":"Cancer Sci."},{"key":"ref_32","doi-asserted-by":"crossref","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":"ref_33","doi-asserted-by":"crossref","first-page":"202905","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":"ref_34","doi-asserted-by":"crossref","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":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","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":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4553","DOI":"10.4049\/jimmunol.1501205","article-title":"Novel insights into the multiple sclerosis risk gene ankrd55","volume":"196","author":"Feliu","year":"2016","journal-title":"J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1177\/1947601913513950","article-title":"Map3k1: Genomic alterations in cancer and function in promoting cell survival or apoptosis","volume":"4","author":"Pham","year":"2013","journal-title":"Genes Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jdcr.2022.05.008","article-title":"Ulerythema ophryogenes in association with map3k1-mutated swyer syndrome","volume":"25","author":"Nimgaonkar","year":"2022","journal-title":"JAAD Case Rep."},{"key":"ref_39","doi-asserted-by":"crossref","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":"ref_40","doi-asserted-by":"crossref","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":"ref_41","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1002\/ijc.29570","article-title":"Integrated pathway and epistasis analysis reveals interactive effect of genetic variants at terf1 and afap1l2 loci on melanoma risk","volume":"137","author":"Brossard","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Zakharov, S., Wong, T.Y., Aung, T., Vithana, E.N., Khor, C.C., Salim, A., and Thalamuthu, A. (2013). Combined genotype and haplotype tests for region-based association studies. BMC Genom., 14.","DOI":"10.1186\/1471-2164-14-569"},{"key":"ref_43","doi-asserted-by":"crossref","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":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1167\/iovs.61.10.37","article-title":"Association of glaucoma risk genes with retinal nerve fiber layer in a multi-ethnic asian population: The singapore epidemiology of eye diseases study","volume":"61","author":"Chai","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/3\/704\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:53:44Z","timestamp":1760122424000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/3\/704"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,13]]},"references-count":44,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["genes14030704"],"URL":"https:\/\/doi.org\/10.3390\/genes14030704","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,13]]}}}