{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T08:41:16Z","timestamp":1780648876145,"version":"3.54.1"},"reference-count":70,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Econom\u00eda y Competitividad-Fondo Europeo de Desarrollo Regional (FEDER)","award":["CIBER 06\/03"],"award-info":[{"award-number":["CIBER 06\/03"]}]},{"name":"Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Econom\u00eda y Competitividad-Fondo Europeo de Desarrollo Regional (FEDER)","award":["RETIC OftaRed"],"award-info":[{"award-number":["RETIC OftaRed"]}]},{"name":"Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Econom\u00eda y Competitividad-Fondo Europeo de Desarrollo Regional (FEDER)","award":["PRX17\/00500"],"award-info":[{"award-number":["PRX17\/00500"]}]},{"name":"University Jaume I","award":["P1-1B2013-54"],"award-info":[{"award-number":["P1-1B2013-54"]}]},{"name":"University Jaume I","award":["COGRUP\/2016\/06"],"award-info":[{"award-number":["COGRUP\/2016\/06"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. The genetics of POAG are complex, and population-specific effects have been reported. Although many polymorphisms associated with POAG risk have been reported, few studies have analyzed their additive effects. We investigated, in a southern European Mediterranean population, the association between relevant POAG polymorphisms, identified by initial genome-wide association studies (GWASs) and POAG risk, both separately and as an aggregated multi-locus genetic risk score (GRS). Also, bearing in mind that oxidative stress is a factor increasingly recognized in the pathogenesis of POAG, we analyzed the potential association of the GRS with plasma concentrations of antioxidant vitamins (C and E). We carried out a case\u2013control study including 391 POAG cases and 383 healthy controls, and analyzed four genetic polymorphisms (rs4656461-TMCO1, rs4236601-CAV1\/CAV2, rs2157719-CDKN2B-AS1 and rs3088440-CDKN2A). An unweighted GRS including the four non-linked polymorphisms was constructed. A strong association between the GRS and POAG risk was found. When three categories of the GRS were considered, subjects in the top category of the GRS were 2.92 (95% confidence interval (CI): 1.79\u20134.77) times more likely to have POAG compared with participants in the bottom category (p &lt; 0.001). Moreover, the GRS was inversely correlated with plasma vitamin C (p = 0.002) and vitamin E (p = 0.001) concentrations, even after additional adjustment for POAG status. In conclusion, we have found a strong association between the GRS and POAG risk in this Mediterranean population. While the additional correlation found between GRS and low levels of vitamins C and E does not indicated a causal relationship, it does suggest the need for new and deeper research into the effects of oxidative stress as a potential mechanism for those associations.<\/jats:p>","DOI":"10.3390\/ijms18112302","type":"journal-article","created":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T16:01:19Z","timestamp":1509552079000},"page":"2302","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["A Multi-Locus Genetic Risk Score for Primary Open-Angle Glaucoma (POAG) Variants Is Associated with POAG Risk in a Mediterranean Population: Inverse Correlations with Plasma Vitamin C and E Concentrations"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1179-1592","authenticated-orcid":false,"given":"Vicente","family":"Zanon-Moreno","sequence":"first","affiliation":[{"name":"Genetic & Molecular Epidemiology Unit, Department of Preventive Medicine & Public Health, School of Medicine, University of Valencia, Avenida Vicente Blasco Ib\u00e1\u00f1ez 15, 46010 Valencia, Spain"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n, Instituto de Salud Carlos III, Calle Sinesio Delgado, 3, 28029 Madrid, Spain"},{"name":"Ophthalmology Research Unit \u201cSantiago Grisolia\u201d, Dr. Peset University Hospital, Avenida Gaspar Aguilar 90, 46017 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Ortega-Azorin","sequence":"additional","affiliation":[{"name":"Genetic & Molecular Epidemiology Unit, Department of Preventive Medicine & Public Health, School of Medicine, University of Valencia, Avenida Vicente Blasco Ib\u00e1\u00f1ez 15, 46010 Valencia, Spain"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n, Instituto de Salud Carlos III, Calle Sinesio Delgado, 3, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Asensio-Marquez","sequence":"additional","affiliation":[{"name":"Genetic & Molecular Epidemiology Unit, Department of Preventive Medicine & Public Health, School of Medicine, University of Valencia, Avenida Vicente Blasco Ib\u00e1\u00f1ez 15, 46010 Valencia, Spain"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n, Instituto de Salud Carlos III, Calle Sinesio Delgado, 3, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Garcia-Medina","sequence":"additional","affiliation":[{"name":"Red Tem\u00e1tica de Investigaci\u00f3n Cooperativa OftaRed, Instituto de Salud Carlos III, Calle Sinesio Delgado, 3, 28029 Madrid, Spain"},{"name":"Department of Ophthalmology, University of Murcia, Campus Universitario de Espinardo Building No. 35, 30100 Murcia, Spain"},{"name":"Department of Ophthalmology, Reina Sofia University General Hospital, Avenida Intendente Jorge Palacios, 1, 30003 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0118-7837","authenticated-orcid":false,"given":"Maria","family":"Pinazo-Duran","sequence":"additional","affiliation":[{"name":"Ophthalmology Research Unit \u201cSantiago Grisolia\u201d, Dr. Peset University Hospital, Avenida Gaspar Aguilar 90, 46017 Valencia, Spain"},{"name":"Red Tem\u00e1tica de Investigaci\u00f3n Cooperativa OftaRed, Instituto de Salud Carlos III, Calle Sinesio Delgado, 3, 28029 Madrid, Spain"},{"name":"Department of Surgery, School of Medicine, University of Valencia, Avenida Vicente Blasco Ib\u00e1\u00f1ez, 15, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Coltell","sequence":"additional","affiliation":[{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n, Instituto de Salud Carlos III, Calle Sinesio Delgado, 3, 28029 Madrid, Spain"},{"name":"Department of Computer Languages and Systems, School of Technology and Experimental Sciences, Universitat Jaume I, Avenida Vicent Sos Baynat s\/n, 12071 Castell\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Ordovas","sequence":"additional","affiliation":[{"name":"Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA"},{"name":"Department of Cardiovascular Epidemiology and Population Genetics, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Calle Melchor Fern\u00e1ndez Almagro, 3, 28029 Madrid, Spain"},{"name":"Instituto Madrile\u00f1o de Estudios Avanzados (IMDEA) Alimentaci\u00f3n, Carretera de Canto Blanco 8-E, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2366-4104","authenticated-orcid":false,"given":"Dolores","family":"Corella","sequence":"additional","affiliation":[{"name":"Genetic & Molecular Epidemiology Unit, Department of Preventive Medicine & Public Health, School of Medicine, University of Valencia, Avenida Vicente Blasco Ib\u00e1\u00f1ez 15, 46010 Valencia, Spain"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n, Instituto de Salud Carlos III, Calle Sinesio Delgado, 3, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16067","DOI":"10.1038\/nrdp.2016.67","article-title":"Primary open-angle glaucoma","volume":"2","author":"Weinreb","year":"2016","journal-title":"Nat. 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