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

doi:10.1016/j.celrep.2013.11.042

Cell Reports (Dec 2013)

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

DOI: https://doi.org/10.1016/j.celrep.2013.11.042
Journal volume & issue: Vol. 5, no. 6
pp. 1527 – 1535

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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