Hypomethylation of the IL17RC Promoter in Peripheral Blood Leukocytes Is Not A Hallmark of Age-Related Macular Degeneration
Verity F. Oliver,
Maria Franchina,
Andrew E. Jaffe,
Kari E. Branham,
Mohammad Othman,
John R. Heckenlively,
Anand Swaroop,
Betsy Campochiaro,
Brendan J. Vote,
Jamie E. Craig,
Richard Saffery,
David A. Mackey,
Jiang Qian,
Donald J. Zack,
Alex W. Hewitt,
Shannath L. Merbs
Affiliations
Verity F. Oliver
Department of Ophthalmology, Wilmer Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA
Maria Franchina
Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, Perth, WA 6009, Australia
Andrew E. Jaffe
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21287, USA
Kari E. Branham
Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA
Mohammad Othman
Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA
John R. Heckenlively
Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA
Anand Swaroop
National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
Betsy Campochiaro
Department of Ophthalmology, Wilmer Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA
Brendan J. Vote
Launceston Eye Institute, University of Tasmania, Launceston 7249, Australia
Jamie E. Craig
Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, SA 5042, Australia
Richard Saffery
Cancer and Disease Epigenetics, Murdoch Childrens Research Institute, University of Melbourne, Royal Children’s Hospital, Melbourne, VIC 3052, Australia
David A. Mackey
Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, Perth, WA 6009, Australia
Jiang Qian
Department of Ophthalmology, Wilmer Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA
Donald J. Zack
Department of Ophthalmology, Wilmer Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA
Alex W. Hewitt
Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, Perth, WA 6009, Australia
Shannath L. Merbs
Department of Ophthalmology, Wilmer Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA
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.