RESUMEN
Age-related macular degeneration (AMD) is a multifactorial genetic disease, with at least 52 identifiable associated gene variants at 34 loci, including variants in complement factor H (CFH) and age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase-1 (ARMS2/HTRA1). Genetic factors account for up to 70% of disease variability. However, population-based genetic risk scores are generally more helpful for clinical trial design and stratification of risk groups than for individual patient counseling. There is some evidence of pharmacogenetic influences on various treatment modalities used in AMD patients, including Age-Related Eye Disease Study (AREDS) supplements, photodynamic therapy (PDT), and anti-vascular endothelial growth factor (anti-VEGF) agents. However, there is currently no convincing evidence that genetic information plays a role in routine clinical care.
Asunto(s)
Degeneración Macular , Proteínas , Humanos , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/genética , Suplementos Dietéticos , Serina Peptidasa A1 que Requiere Temperaturas Altas/genética , Factores de Crecimiento Endotelial Vascular/genética , Factores de Crecimiento Endotelial Vascular/uso terapéutico , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
Age-related macular degeneration (AMD) is a leading cause of irreversible visual loss and is primarily treated with nutritional supplementation as well as with anti-vascular endothelial growth factor (VEGF) agents for certain patients with neovascular disease. AMD is a complex disease with both genetic and environmental risk factors. In addition, treatment outcomes from nutritional supplementation and anti-VEGF agents vary considerably. Therefore, it is reasonable to suspect that there may be pharmacogenetic influences on these treatments. Many series have reported individual associations with variants in complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2), and other loci. However, at this time there are no validated associations. With respect to AMD, pharmacogenetics remains an intriguing area of research but is not helpful for routine clinical management.
Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Suplementos Dietéticos , Degeneración Macular/tratamiento farmacológico , Farmacogenética , Factores de Edad , Humanos , Degeneración Macular/genética , Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
PURPOSE: To determine if short-term Age-Related Eye Disease Study (AREDS) antioxidant and zinc supplementation affects biomarkers of oxidative stress, possibly serving as a predictor of their efficacy. DESIGN: Prospective interventional case series. METHODS: Nineteen subjects, 12 with intermediate or advanced age-related macular degeneration (AMD) (AREDS categories 3 or 4) and 7 non-AMD controls, were admitted to the Vanderbilt General Clinical Research Center and placed on a controlled diet for 7 days. Antioxidant and zinc supplements were stopped 2 weeks prior to study enrollment. Dietary supplementation with 500 mg vitamin C, 400 IU vitamin E, 15 mg ß-carotene, 80 mg zinc oxide, and 2 mg cupric oxide per day was instituted on study day 2. Blood was drawn on study days 2 and 7, and plasma concentrations of cysteine (Cys), cystine (CySS), glutathione (GSH), isoprostane (IsoP), and isofuran (IsoF) were determined. RESULTS: Short-term AREDS supplementation significantly lowered mean plasma levels of CySS in participants on a regulated diet (P = .034). No significant differences were observed for Cys, GSH, IsoP, or IsoF. There were no significant differences between AMD patients and controls. CONCLUSIONS: This pilot interventional study shows that a 5-day course of antioxidant and zinc supplements can modify plasma levels of CySS, suggesting that this oxidative stress biomarker could help predict how likely an individual is to benefit from AREDS supplementation. Further, CySS may be useful for the evaluation of new AMD therapies, particularly those hypothesized to affect redox status.
Asunto(s)
Antioxidantes/administración & dosificación , Biomarcadores/sangre , Cisteína/sangre , Degeneración Macular/tratamiento farmacológico , Estrés Oxidativo , Óxido de Zinc/administración & dosificación , Anciano , Ácido Ascórbico/administración & dosificación , Cobre/administración & dosificación , Cistina/sangre , Suplementos Dietéticos , Femenino , Furanos/sangre , Glutatión/sangre , Humanos , Isoprostanos/sangre , Degeneración Macular/sangre , Masculino , Proyectos Piloto , Estudios Prospectivos , Vitamina E/administración & dosificación , beta Caroteno/administración & dosificaciónRESUMEN
EVALUATION OF: Klein ML, Francis PJ, Rosner B et al.: CFH and LOC387715/ARMS2 genotypes and treatment with antioxidants and zinc for age-related macular degeneration. Ophthalmology 115(6), 1019-1025 (2008). The late form of age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly, with a complex etiology involving genetic and environmental factors. Recently, multiple distinct genetic susceptibility loci for AMD have been identified. Specifically, variations in the Complement Factor H (CFH) gene as well as the LOC387715/ARMS2 gene have been shown to be strongly associated with AMD. The Age-Related Eye Disease Study (AREDS) is a large multicenter, placebo-controlled, randomized clinical trial that showed that a combination of zinc and antioxidants reduced progression to late-stage AMD. In the present study, the authors found that within AREDS there was a significant interaction between zinc and CFH genotypes, indicating that CFH genotypes may be predictive of treatment response to zinc supplementation.