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
| Autor: | Zanon-Moreno V, Ortega-Azorin C, Asensio-Marquez EM, Garcia-Medina JJ, Pinazo-Duran MD, Coltell O, Ordovas JM, Corella D |
|---|---|
| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES r-FISABIO. Repositorio Institucional de Producción Científica instname r-FISABIO: Repositorio Institucional de Producción Científica Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO) |
| ISSN: | 1661-6596 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|