2024-03-29T10:38:03Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/72602022-10-13T08:56:44Zcom_20.500.12105_2145com_20.500.12105_2051com_20.500.12105_2144col_20.500.12105_2146
Repisalud
author
Zanon-Moreno, Vicente
author
Ortega-Azorin, Carolina
author
Asensio-Marquez, Eva M
author
Garcia-Medina, Jose J
author
Pinazo-Duran, Maria D
author
Coltell, Oscar
author
Ordovas, Jose M
author
Corella, Dolores
funder
Ministerio de Sanidad, Consumo y Bienestar Social (España)
funder
Ministerio de Economía y Competitividad (España)
funder
Instituto de Salud Carlos III
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Centro de Investigación Biomedica en Red - CIBER
funder
Jaume I University (España)
2019-02-28T15:44:19Z
2019-02-28T15:44:19Z
2017-11-01
Int J Mol Sci. 2017; 18(11):E2302
1422-0067
http://hdl.handle.net/20.500.12105/7260
29104244
10.3390/ijms18112302
1422-0067
International journal of molecular sciences
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.
eng
GWAS
Genetic risk score
Genetics
Nutrition
Primary open-angle glaucoma
Vitamin C
Vitamin E
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
journal article
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https://repisalud.isciii.es/bitstream/20.500.12105/7260/1/AMulti-LocusGeneticRiskScore%20_2017.pdf
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AMulti-LocusGeneticRiskScore _2017.pdf
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AMulti-LocusGeneticRiskScore _2017.pdf.txt
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https://repisalud.isciii.es/bitstream/20.500.12105/7260/6/AMulti-LocusGeneticRiskScore%20_2017_SM.pdf.txt
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AMulti-LocusGeneticRiskScore _2017_SM.pdf.txt