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

International Journal of Molecular Sciences

Oscar Coltell¹  Eva M. Asensio-Marquez²  Vicente Zanon-Moreno²  Dolores Corella²  Carolina Ortega-Azorin²  Jose M. Ordovas³  Maria D. Pinazo-Duran⁴  Jose J. Garcia-Medina⁵ 

[1] CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Calle Sinesio Delgado, 3, 28029 Madrid, Spain;Genetic & Molecular Epidemiology Unit, Department of Preventive Medicine & Public Health, School of Medicine, University of Valencia, Avenida Vicente Blasco Ibáñez 15, 46010 Valencia, Spain;Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA;Ophthalmology Research Unit “Santiago Grisolia”, Dr. Peset University Hospital, Avenida Gaspar Aguilar 90, 46017 Valencia, Spain;Red Temática de Investigación Cooperativa OftaRed, Instituto de Salud Carlos III, Calle Sinesio Delgado, 3, 28029 Madrid, Spain;

关键词: primary open-angle glaucoma;    genetics;    GWAS;    nutrition;    vitamin C;    vitamin E;    genetic risk score;   

DOI  :  10.3390/ijms18112302

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown