Hypomethylation of the IL17RC Promoter Associates with Age-Related Macular Degeneration

SummaryAge-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly population worldwide. Although recent studies have demonstrated strong genetic associations between AMD and SNPs in a number of genes, other modes of regulation are also likely to play a role in the etiology of this disease. We identified a significantly decreased level of methylation on the IL17RC promoter in AMD patients. Furthermore, we showed that hypomethylation of the IL17RC promoter in AMD patients led to an elevated expression of its protein and messenger RNA in peripheral blood as well as in the affected retina and choroid, suggesting that the DNA methylation pattern and expression of IL17RC may potentially serve as a biomarker for the diagnosis of AMD and likely plays a role in disease pathogenesis.

Graphical AbstractFigure optionsDownload as PowerPoint slideHighlights
► ∼1.5% of CpG sites are differentially methylated between twins with discordant AMD
► Hypomethylated IL17RC promoter and elevated IL17RC expression are associated with AMD
► IL-17-mediated inflammatory responses contribute to AMD pathogenesis