Dataset Information

Plasma biomarkers of oxidative stress and genetic variants in age-related macular degeneration.

ABSTRACT:

Purpose

To compare plasma levels of oxidative stress biomarkers in patients with age-related macular degeneration (AMD) and controls and to evaluate a potential relationship between biochemical markers of oxidative stress and AMD susceptibility genotypes.

Design

Prospective case-control study.

Methods

Plasma levels of oxidative stress biomarkers were determined in 77 AMD patients and 75 controls recruited from a clinical practice. Cysteine, cystine (CySS), glutathione, isoprostane, and isofuran were measured, and participants were genotyped for polymorphisms in the complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genes.

Results

CySS was elevated in cases compared with controls (P = .013). After adjustment for age, sex, and smoking, this association was not significant. In all participants, CySS levels were associated with the CFH polymorphism rs3753394 (P = .028) as well as an 8-allele CFH haplotype (P = .029) after correction for age, gender, and smoking. None of the other plasma markers was related to AMD status in our cohort.

Conclusions

Our investigation of the gene-environment interaction involved in AMD revealed a relationship between a plasma biomarker of oxidative stress, CySS, and CFH genotype. These data suggest a potential association between inflammatory regulators and redox status in AMD pathogenesis.

SUBMITTER: Brantley MA

PROVIDER: S-EPMC3288635 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Publications

Plasma biomarkers of oxidative stress and genetic variants in age-related macular degeneration.

Brantley Milam A MA Osborn Melissa P MP Sanders Barton J BJ Rezaei Kasra A KA Lu Pengcheng P Li Chun C Milne Ginger L GL Cai Jiyang J Sternberg Paul P

American journal of ophthalmology 20111029 3

<h4>Purpose</h4>To compare plasma levels of oxidative stress biomarkers in patients with age-related macular degeneration (AMD) and controls and to evaluate a potential relationship between biochemical markers of oxidative stress and AMD susceptibility genotypes.<h4>Design</h4>Prospective case-control study.<h4>Methods</h4>Plasma levels of oxidative stress biomarkers were determined in 77 AMD patients and 75 controls recruited from a clinical practice. Cysteine, cystine (CySS), glutathione, isop ...[more]

PMID: 22035603

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Project description:Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD is characterized by the appearance of soft drusen, as well as pigmentary changes in the retinal pigment epithelium (RPE). These soft, confluent drusen can progress into two forms of advanced AMD: geographic atrophy (GA, or dry AMD) or choroidal neovascularization (CNV, or wet AMD). Both forms of AMD result in a similar clinical progression in terms of loss of central vision. The exact mechanism for developing early AMD, as well as triggers responsible for progressing to advanced stage of disease, is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as causes of AMD progression. Multiple genes and/or single nucleotide polymorphisms (SNPs) have been found associated with AMD, including various genes involved in the complement pathway, lipid metabolism and extracellular matrix (ECM) remodeling. Of the known genetic contributors to disease risk, the CFH Y402H and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress plays a critical role in many aging diseases including cardiovascular disease, cancer, Alzheimer's disease and AMD. Due to the exposure to sunlight and high oxygen concentration, the oxidative stress burden is higher in the eye than other tissues, which can be further complicated by additional oxidative stressors such as smoking. Increasingly, evidence is accumulating suggesting that functional abnormalities of the innate immune system incurred via high risk genotypes may be contributing to the pathogenesis of AMD by altering the inflammatory homeostasis in the eye, specifically in the handling of oxidation products. As the eye in non-pathological instances maintains a low level of inflammation despite the presence of a relative abundance of potentially inflammatory molecules, we have previously hypothesized that the tight homeostatic control of inflammation via the innate immune system is likely critical for avoidance of disease progression. However, the presence of a multitude of potential triggers of inflammation results in a sensitive balance in which perturbations thereof would subsequently alter the inflammatory state of the retina, leading to a state of chronic inflammation and pathologic progression. In this review, we will highlight the background literature surrounding the known genetic and environmental contributors to AMD risk, as well as a discussion of the potential mechanistic interplay of these factors that lead to disease pathogenesis with particular emphasis on the delicate control of inflammatory homeostasis and the centrality of the innate immune system in this process.

Dataset Information

Plasma biomarkers of oxidative stress and genetic variants in age-related macular degeneration.

Purpose

Design

Methods

Results

Conclusions

Publications

Plasma biomarkers of oxidative stress and genetic variants in age-related macular degeneration.

Similar Datasets

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