Mutation Analysis of Oxisterol-Binding-Protein Gene in Patients with Age-Related Macular Degeneration

Abstract

Allelic variants of several genes are increasingly recognized as susceptibility factors in age-related macular degeneration (AMD). Because of its metabolic characteristics the macula is sensitive to oxidative damage, and supplementation with antioxidants has been shown to be effective in slowing the progression of disease in AMD patients. The oxisterol-binding-protein (OSBP2) gene is expressed mainly in the retinal pigmented epithelium underlying the macular region. Its product specifically binds and transports oxisterols, the cytotoxic effects of which may be involved in macular damage. The aim of this study was to search for allelic variants of OSBP2 gene, as well as to evaluate several risk factors in 24 patients with AMD; 17 with nonexudative (NE) and 7 with neovascular (NV) form. Total cholesterol was elevated in 66% of the patients, high-density lipoprotein (HDL) cholesterol was reduced in 12%; vitamin A or vitamin E deficiency was not observed. OSBP2 gene analysis was performed in AMD patients and in 110 control subjects by single-stranded conformational polymorphism (SSCP) analysis followed by direct sequencing. Six allelic variants were detected: 2 nonpolymorphic unique exonic variants in 2 AMD subjects and 4 polymorphic variants (2 exonic and 2 intronic). These data indicate a possible role of OSBP2 gene in the pathogenesis of oxidative damage to the macula induced by oxysterols in AMD patients.

Cholesterol oxidation in the retina: implications of 7KCh formation in chronic inflammation and age-related macular degeneration

“…AMD is foremost an aging disease that undoubtedly has very signifi cant genetic and environmental risk factors (143)(144)(145)(146). The age-related factor(s) in the pathogenesis of AMD will likely be the key to the treatment and/or prevention of this disease.…”

“…Genetic studies are beginning to support the involvement of lipid-related genes with AMD. OSBP2, which binds 7KCh and is highly expressed in the retina ( 81 ), has been genetically linked to AMD ( 145 ). A recent genomewide association study has linked hepatic lipase C, CETP, and ABCA1 to AMD ( 146 ).…”

Subdivision of molecularly-classified groups by new gene signatures in breast cancer patients

“…The remaining 16 are not directly associated with cancer development (20)(21)(22)(23)(24) (Table V). These genes are involved in certain pathways, such as p53 protein stabilisation, the ubiquitin proteosome pathway, angiogenesis, cell survival and proliferation, G2 to M transition and protein synthesis, where defects in each of these may lead, indirectly, to cancer development (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37). Our data suggests that some of these genes, not solely but as parts of a classifier can be used for the prognosis of breast cancer.…”

Endoplasmic reticulum stress: molecular mechanism and therapeutic targets

“…Nucleotide changes in the oxysterol-binding protein, including c.347A>G, c.450G>T, and c.2351G>A, are found in patients with dry AMD. 281 Single-nucleotide polymorphisms in CXCL3 are risk variants for AMD. 282 ERp29 deficiency resulting in protein accumulation in CCL2 −/− /CX3CR1 −/− mouse models might explain the ER stress activation and related AMD.…”