{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:48:44Z","timestamp":1785836924405,"version":"3.56.0"},"reference-count":32,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007329","name":"Universidad del Valle","doi-asserted-by":"publisher","award":["1903"],"award-info":[{"award-number":["1903"]}],"id":[{"id":"10.13039\/501100007329","id-type":"DOI","asserted-by":"publisher"}]},{"award":["1903"],"award-info":[{"award-number":["1903"]}],"id":[{"id":"https:\/\/ror.org\/00jb9vg53","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Primary open-angle glaucoma (POAG) is a complex multifactorial optic neuropathy involving genetic, vascular, oxidative, inflammatory, and neurodegenerative mechanisms. Despite advances in genome-wide studies, the contribution of genetic variants remains incompletely characterized in underrepresented Latin American populations. This study aimed to characterize the genetic landscape of POAG in a Colombian cohort by identifying previously reported glaucoma-associated variants, rare candidate variants, and pharmacogenomic markers and integrating these findings into biologically relevant pathways. Methods: An exploratory descriptive study was conducted in 21 Colombian patients with confirmed POAG. Whole-exome sequencing (WES) was performed at an average sequencing depth of approximately 100\u00d7. Variants were quality-filtered, functionally annotated, and prioritized within 446 POAG-associated genes retrieved from DisGeNET. Previously reported glaucoma-associated variants and rare candidate variants were identified, while pharmacogenomic variants related to latanoprost and timolol response were evaluated using ClinPGx\/PharmGKB. Identified genes were classified according to major biological pathways relevant to glaucoma pathophysiology. Results: Of the 446 POAG-associated genes, 381 were detected in the patients\u2019 exomes. A total of 10,220 molecular variants were identified, of which 1,187 synonymous variants were excluded, leaving 9,033 variants for downstream analysis. Among these, 955 were non-synonymous SNVs, including 26 variants previously reported in association with glaucoma and 929 potentially novel coding variants. Previously reported variants included loci in SIX6, LOXL1, CYP1B1, NOS3, and SOD2. Two rare candidate variants (minor allele frequency &lt;1%) were identified in FMNL2 and C3. Pharmacogenomic variants in PTGS1, ADRB1, and ABCC4 with potential implications for response to latanoprost or timolol were also detected. Functional integration highlighted pathways involving oxidative stress, extracellular matrix remodeling, vascular regulation, neurodegeneration, and inflammation. Conclusions: This exploratory analysis identifies known glaucoma-associated variants, rare candidate variants, and pharmacogenomic markers in Colombian patients with POAG. The findings support a multifactorial biological framework involving interconnected oxidative, structural, vascular, neurodegenerative, and inflammatory pathways. The FMNL2 and C3 variants represent candidates for further investigation, while the identified pharmacogenomic variants highlight the potential relevance of genomic profiling for personalized glaucoma management. Larger ancestry-informed case\u2013control studies are required to validate these observations and determine their clinical significance.<\/jats:p>","DOI":"10.3390\/genes17080919","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:15:22Z","timestamp":1785834922000},"page":"919","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploratory Analysis of Glaucoma-Associated SNPs in a Colombian Cohort Highlights Potential Involvement of Oxidative, Vascular, and Neurodegenerative Pathways"],"prefix":"10.3390","volume":"17","author":[{"given":"Carlos","family":"Casanova","sequence":"first","affiliation":[{"name":"TAOLab-OneHealth, Faculty of Natural & Exact Sciences, Universidad del Valle, Cali 760032, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Valencia-Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Faculty of Health, Universidad del Valle, Cali 760043, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7815-4390","authenticated-orcid":false,"given":"Wilmar","family":"Saldarriaga-Gil","sequence":"additional","affiliation":[{"name":"Faculty of Health, Universidad del Valle, Cali 760043, Colombia"},{"name":"Hospital Universitario del Valle, Cali 760042, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Lozano-Cruz","sequence":"additional","affiliation":[{"name":"Faculty of Health, Universidad del Valle, Cali 760043, Colombia"},{"name":"Cl\u00ednica de Oftalmolog\u00eda de Cali, Cali 760036, Colombia"},{"name":"Cl\u00ednica Vision IA, Cali 760046, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9006-6721","authenticated-orcid":false,"given":"Andr\u00e9s","family":"Castillo","sequence":"additional","affiliation":[{"name":"TAOLab-OneHealth, Faculty of Natural & Exact Sciences, Universidad del Valle, Cali 760032, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref_1","first-page":"668","article-title":"Glaucoma","volume":"93","author":"Gupta","year":"2016","journal-title":"Am. Fam. Physician."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1136\/bjo.2005.081224","article-title":"The number of people with glaucoma worldwide in 2010 and 2020","volume":"90","author":"Quigley","year":"2006","journal-title":"Br. J. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.2147\/OPTH.S165747","article-title":"Blood pressure, ocular perfusion pressure and open-angle glaucoma in patients with systemic hypertension","volume":"12","author":"Cantor","year":"2018","journal-title":"Clin. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6509809","DOI":"10.1155\/2016\/6509809","article-title":"Medical Management of Glaucoma in the 21st Century from a Canadian Perspective","volume":"2016","author":"Harasymowycz","year":"2016","journal-title":"J. Ophthalmol."},{"key":"ref_5","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":"J. Am. Med. Assoc."},{"key":"ref_6","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_7","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/ceo.14035","article-title":"The genetics of glaucoma: Disease associations, personalised risk assessment and therapeutic opportunities-A review","volume":"50","author":"Aboobakar","year":"2022","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1002\/mgg3.139","article-title":"Genetics and genomic medicine in Colombia","volume":"3","author":"Restrepo","year":"2015","journal-title":"Mol. Genet. Genomic Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/0165-6147(91)90516-U","article-title":"Interethnic variation of drug metabolism","volume":"12","author":"Kalow","year":"1991","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"267","DOI":"10.2165\/11588830-000000000-00000","article-title":"Effects of common topical antiglaucoma medications on the ocular surface, eyelids and periorbital tissue","volume":"28","author":"Servat","year":"2011","journal-title":"Drugs Aging"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s13062-023-00423-4","article-title":"Effect of genotype on individual response to the pharmacological treatment of glaucoma: A systematic review and meta-analysis","volume":"18","author":"Scuteri","year":"2023","journal-title":"Biol. Direct"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1002\/cpt.2350","article-title":"An Evidence-Based Framework for Evaluating Pharmacogenomics Knowledge for Personalized Medicine","volume":"110","author":"Huddart","year":"2021","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.preteyeres.2011.05.001","article-title":"Acute retinal arterial occlusive disorders","volume":"30","author":"Hayreh","year":"2011","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/bioinformatics\/btp698","article-title":"Fast and accurate long-read alignment with Burrows-Wheeler transform","volume":"26","author":"Li","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: Functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_17","first-page":"D845","article-title":"The DisGeNET knowledge platform for disease genomics: 2019 update","volume":"48","author":"Ronzano","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1093\/hmg\/ddt522","article-title":"Exome sequencing and functional analyses suggest that SIX6 is a gene involved in an altered proliferation-differentiation balance early in life and optic nerve degeneration at old age","volume":"23","author":"Iglesias","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1126\/science.1146554","article-title":"Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma","volume":"317","author":"Thorleifsson","year":"2007","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.exer.2016.07.011","article-title":"Trabecular meshwork stiffness in glaucoma","volume":"158","author":"Wang","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3426","DOI":"10.1016\/j.cell.2022.08.004","article-title":"High-coverage whole-genome sequencing of the expanded 1000 Genomes Project cohort including 602 trios","volume":"185","author":"Evani","year":"2022","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"a017269","DOI":"10.1101\/cshperspect.a017269","article-title":"The complex role of neuroinflammation in glaucoma","volume":"4","author":"Soto","year":"2014","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s00228-014-1769-8","article-title":"Influence of PTGS1, PTGFR, and MRP4 genetic variants on intraocular pressure response to latanoprost in Chinese primary open-angle glaucoma patients","volume":"71","author":"Gao","year":"2015","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1007\/s00228-005-0052-4","article-title":"Polymorphisms of genes CYP2D6, ADRB1 and GNAS1 in pharmacokinetics and systemic effects of ophthalmic timolol. A pilot study","volume":"61","author":"Nieminen","year":"2005","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7537","DOI":"10.1038\/sj.onc.1206953","article-title":"The MRP family of drug efflux pumps","volume":"22","author":"Kruh","year":"2003","journal-title":"Oncogene"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1126\/science.aal0092","article-title":"Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice","volume":"355","author":"Williams","year":"2017","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.exer.2014.07.014","article-title":"Extracellular matrix in the trabecular meshwork: Intraocular pressure regulation and dysregulation in glaucoma","volume":"133","author":"Vranka","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S1350-9462(02)00008-3","article-title":"The impact of ocular blood flow in glaucoma","volume":"21","author":"Flammer","year":"2002","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"101261","DOI":"10.1016\/j.preteyeres.2024.101261","article-title":"Addressing neurodegeneration in glaucoma: Mechanisms, challenges, and treatments","volume":"100","author":"Wareham","year":"2024","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.exer.2010.07.009","article-title":"The immune response in glaucoma: A perspective on the roles of oxidative stress","volume":"93","author":"Tezel","year":"2011","journal-title":"Exp. Eye Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1146\/annurev.neuro.051508.135728","article-title":"Under pressure: Cellular and molecular responses during glaucoma, a common neurodegeneration with axonopathy","volume":"35","author":"Nickells","year":"2012","journal-title":"Annu. Rev. Neurosci."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/8\/919\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:40:46Z","timestamp":1785836446000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/8\/919"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":32,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["genes17080919"],"URL":"https:\/\/doi.org\/10.3390\/genes17080919","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,4]]}}}