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Nickisa Hodgson, Ken Flagg, David Granet, Bobby S. Korn, Don O. Kikkawa, Kang Zhang; Epigenetic Variants of Distinct Clinical Features of Thyroid Eye Disease. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4815. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
This study examines the epigenetic variants associated with distinct clinical features of thyroid eye disease (TED). Alterations in DNA methylation and epigenetic variants may contribute to the development of clinical features of TED.
A total of 49 patients were enrolled and whole blood samples were obtained in this study. Patients were categorized into presence or absence of: exophthalmos; eyelid retraction; and restrictive myopathy. Samples were processed with the Infinium Human Methylation 450 Bead Chip assay, which measures the methylation states of 485,577 CpG markers. Methylation data were analyzed as a fraction between zero and one, representing the frequency of methylation of a given CpG marker across the population of blood cells taken from a single individual. 485,577 markers were compared independently between cases of thyroid eye disease with and without exophthalmos, restrictive myopathy, and eyelid retraction using the colttests function in the R gene filter package. Statistical analysis was performed using R.
Of 49 patients, 44 patients (89%) had exophthalmos, 31 patients (63%) had restrictive myopathy, and 33 patients (67%) had eyelid retraction (Figure 1). Methylation of marker cg24865007 was found to have a methylation fraction difference of 5% more in cases of exophthalmos versus without exophthalmos (P < 4.4xE-08). DNA methylation of this marker on gene KIR2DS4 on chromosome 19 remains significant (P < .02) after adjusting for all comparisons by Bonferonni correction. Methylation of marker cg26876701 had a methylation fraction of greater than 5% more in cases with restrictive myopathy versus without restrictive myopathy (P < 9.2xE-07). DNA methylation of this marker on gene SMAD3 on chromosome 15 is not significant after adjusting for all comparisons (P < .44). There were no significant markers associated with eyelid retraction.
TED related exophthalmos has a significant methylation difference compared with TED without exophthalmos of gene KIR2DS4 (Killer cell immunoglobulin-like receptor), a glycoprotein expressed by T cells and natural killer cells which plays an important role in immune regulation. Restrictive myopathy is associated with methylation of SMAD3, a transcriptional modulator activated by transforming growth factor-beta (TGF-β), however this was not significant after adjusting for multiple comparisons.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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