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Cell Rep. 2013 Dec 26;5(6):1527-35. doi: 10.1016/j.celrep.2013.11.042.

Hypomethylation of the IL17RC promoter in peripheral blood leukocytes is not a hallmark of age-related macular degeneration.

Author information

1
Department of Ophthalmology, Wilmer Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA.
2
Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, Perth, WA 6009, Australia.
3
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21287, USA.
4
Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA.
5
National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
6
Launceston Eye Institute, University of Tasmania, Launceston 7249, Australia.
7
Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, SA 5042, Australia.
8
Cancer and Disease Epigenetics, Murdoch Childrens Research Institute, University of Melbourne, Royal Children's Hospital, Melbourne, VIC 3052, Australia.
9
Department of Ophthalmology, Wilmer Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA; Department of Molecular Biology and Genetics, Department of Neuroscience, and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA; Institut de la Vision, Université Pierre et Marie Curie, Paris 75012, France.
10
Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, Perth, WA 6009, Australia; Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC 3002, Australia. Electronic address: hewitt.alex@gmail.com.
11
Department of Ophthalmology, Wilmer Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA. Electronic address: smerbs@jhmi.edu.

Abstract

Age-related macular degeneration (AMD) is a leading cause of visual impairment worldwide. Aberrant DNA methylation within the promoter of IL17RC in peripheral blood mononuclear cells has recently been reported in AMD. To validate this association, we examined DNA methylation of the IL17RC promoter in peripheral blood. First, we used Illumina Human Methylation450 Bead Arrays, a widely accepted platform for measuring global DNA methylation. Second, methylation status at multiple sites within the IL17RC promoter was determined by bisulfite pyrosequencing in two cohorts. Third, a methylation-sensitive quantitative PCR-based assay was performed on a subset of samples. In contrast to previous findings, we did not find evidence of differential methylation between AMD cases and age-matched controls. We conclude that hypomethylation within the IL17RC gene promoter in peripheral blood is not suitable for use as a clinical biomarker of AMD. This study highlights the need for considerable replication of epigenetic association studies prior to clinical application.

PMID:
24373284
PMCID:
PMC3926096
DOI:
10.1016/j.celrep.2013.11.042
[Indexed for MEDLINE]
Free PMC Article
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