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Int. J. Mol. Sci. 2017, 18(11), 2302; https://doi.org/10.3390/ijms18112302

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

1
Genetic & Molecular Epidemiology Unit, Department of Preventive Medicine & Public Health, School of Medicine, University of Valencia, Avenida Vicente Blasco Ibáñez 15, 46010 Valencia, Spain
2
CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Calle Sinesio Delgado, 3, 28029 Madrid, Spain
3
Ophthalmology Research Unit “Santiago Grisolia”, Dr. Peset University Hospital, Avenida Gaspar Aguilar 90, 46017 Valencia, Spain
4
Red Temática de Investigación Cooperativa OftaRed, Instituto de Salud Carlos III, Calle Sinesio Delgado, 3, 28029 Madrid, Spain
5
Department of Ophthalmology, University of Murcia, Campus Universitario de Espinardo Building No. 35, 30100 Murcia, Spain
6
Department of Ophthalmology, Reina Sofia University General Hospital, Avenida Intendente Jorge Palacios, 1, 30003 Murcia, Spain
7
Department of Surgery, School of Medicine, University of Valencia, Avenida Vicente Blasco Ibáñez, 15, 46010 Valencia, Spain
8
Department of Computer Languages and Systems, School of Technology and Experimental Sciences, Universitat Jaume I, Avenida Vicent Sos Baynat s/n, 12071 Castellón, Spain
9
Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA
10
Department of Cardiovascular Epidemiology and Population Genetics, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Calle Melchor Fernández Almagro, 3, 28029 Madrid, Spain
11
Instituto Madrileño de Estudios Avanzados (IMDEA) Alimentación, Carretera de Canto Blanco 8-E, 28049 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Received: 17 September 2017 / Revised: 25 October 2017 / Accepted: 29 October 2017 / Published: 1 November 2017
(This article belongs to the Collection Human Single Nucleotide Polymorphisms and Disease Diagnostics)
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Abstract

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–control 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): 1.79–4.77) times more likely to have POAG compared with participants in the bottom category (p < 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. View Full-Text
Keywords: primary open-angle glaucoma; genetics; GWAS; nutrition; vitamin C; vitamin E; genetic risk score primary open-angle glaucoma; genetics; GWAS; nutrition; vitamin C; vitamin E; genetic risk score
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Zanon-Moreno, V.; Ortega-Azorin, C.; Asensio-Marquez, E.M.; Garcia-Medina, J.J.; Pinazo-Duran, M.D.; Coltell, O.; Ordovas, J.M.; Corella, D. 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. Int. J. Mol. Sci. 2017, 18, 2302.

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