Hypomethylation of the IL17RC Promoter in Peripheral Blood Leukocytes Is Not A Hallmark of Age-Related Macular Degeneration

Verity Oliver; Maria Franchina; Andrew Jaffe; Kari Branham; Mohammad Othman; John Heckenlively; Anand Swaroop; Betsy Campochiaro; Brendan Jt Vote; Jamie Craig; Richard Saffery; David Mackey; Jiang Qian; D Zack; Alex Hewitt; Shannath Merbs

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

Verity Oliver, Maria Franchina, Andrew Jaffe, Kari Branham, Mohammad Othman, John Heckenlively, Anand Swaroop, Betsy Campochiaro, Brendan Jt Vote, Jamie Craig, Richard Saffery, David Mackey, Jiang Qian, D Zack, Alex Hewitt, Shannath Merbs

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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.

Original language	English
Pages (from-to)	1527-1535
Number of pages	9
Journal	Cell Reports
Volume	5
Issue number	6
DOIs	https://doi.org/10.1016/j.celrep.2013.11.042
Publication status	Published - 26 Dec 2013

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Oliver, V., Franchina, M., Jaffe, A., Branham, K., Othman, M., Heckenlively, J., Swaroop, A., Campochiaro, B., Vote, B. J., Craig, J., Saffery, R., Mackey, D., Qian, J., Zack, D., Hewitt, A., & Merbs, S. (2013). Hypomethylation of the IL17RC Promoter in Peripheral Blood Leukocytes Is Not A Hallmark of Age-Related Macular Degeneration. Cell Reports, 5(6), 1527-1535. https://doi.org/10.1016/j.celrep.2013.11.042

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title = "Hypomethylation of the IL17RC Promoter in Peripheral Blood Leukocytes Is Not A Hallmark of Age-Related Macular Degeneration",

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.",

author = "Verity Oliver and Maria Franchina and Andrew Jaffe and Kari Branham and Mohammad Othman and John Heckenlively and Anand Swaroop and Betsy Campochiaro and Vote, {Brendan Jt} and Jamie Craig and Richard Saffery and David Mackey and Jiang Qian and D Zack and Alex Hewitt and Shannath Merbs",

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Oliver, V, Franchina, M, Jaffe, A, Branham, K, Othman, M, Heckenlively, J, Swaroop, A, Campochiaro, B, Vote, BJ, Craig, J, Saffery, R, Mackey, D, Qian, J, Zack, D, Hewitt, A & Merbs, S 2013, 'Hypomethylation of the IL17RC Promoter in Peripheral Blood Leukocytes Is Not A Hallmark of Age-Related Macular Degeneration', Cell Reports, vol. 5, no. 6, pp. 1527-1535. https://doi.org/10.1016/j.celrep.2013.11.042

TY - JOUR

T1 - Hypomethylation of the IL17RC Promoter in Peripheral Blood Leukocytes Is Not A Hallmark of Age-Related Macular Degeneration

AU - Oliver, Verity

AU - Franchina, Maria

AU - Jaffe, Andrew

AU - Branham, Kari

AU - Othman, Mohammad

AU - Heckenlively, John

AU - Swaroop, Anand

AU - Campochiaro, Betsy

AU - Vote, Brendan Jt

AU - Craig, Jamie

AU - Saffery, Richard

AU - Mackey, David

AU - Qian, Jiang

AU - Zack, D

AU - Hewitt, Alex

AU - Merbs, Shannath

PY - 2013/12/26

Y1 - 2013/12/26

N2 - 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.

AB - 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.

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JO - Cell Reports

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IS - 6

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Hypomethylation of the IL17RC Promoter in Peripheral Blood Leukocytes Is Not A Hallmark of Age-Related Macular Degeneration

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