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Milam A. Brantley, Jr., Jiyang Cai, Melissa P. Osborn, Barton J. Sanders, Pengcheng Lu, Chun Li, Jonathan L. Haines, Paul Sternberg, Jr.; Biomarkers of Oxidative Stress and Genetic Variants in Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3068.
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Oxidative stress has been implicated in the pathogenesis of age-related macular degeneration (AMD). Two primary risk factors for AMD, aging and smoking, correspond to increased levels of free radicals and thus oxidative stress. In addition to diet and environment, genetics influences AMD susceptibility. Polymorphisms in the complement factor H (CFH) and ARMS2 genes have been consistently linked with AMD. The purpose of this study is to evaluate a potential relationship between biochemical markers of oxidative stress and AMD susceptibility genotypes.
Plasma levels of oxidative stress biomarkers were measured in 152 participants, 77 with AMD and 75 non-AMD controls, recruited from the Vanderbilt Eye Institute. To assess plasma thiol redox, glutathione (GSH), cysteine (Cys), and cystine (CySS) were measured by high performance liquid chromatography, and the redox potential of Cys/CySS was calculated. To evaluate the effects of lipid peroxidation, plasma isoprostane (isoP) and isofuran (isoF) were measured using gas chromatography/mass spectrometry. All participants were genotyped for single nucleotide polymorphisms (SNPs) in the CFH and ARMS2 genes.
In our study population, plasma levels of CySS were higher in AMD patients than controls (p = 0.013). After adjusting for age, gender, and SNPs in CFH and ARMS2, the association was no longer significant. CySS levels in all subjects were found to be associated with CFH SNP rs3753394 (p = 0.006) as well as an eight-allele CFH haplotype (p = 0.020) after correction for age, gender, and smoking. None of the other markers was related to AMD status in our cohort.
Our investigation of the gene/environment interaction involved in AMD revealed a relationship between a blood plasma biomarker of antioxidant status, cystine, and CFH genotype. These results suggest a potential relationship between inflammatory regulators and the role of redox status in the pathogenesis of AMD.
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