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Paul N. Baird, Mohamed Dirani, Andrea J. Richardson, Maria Schache, Julia Morahan, George C. Ebers, Robyn H. Guymer, Sreeram V. Ramagopalan; An Epigenetic Study of Monozygotic Twin Pairs Discordant for Birth-Weight. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3310.
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Increased weight has been implicated as a risk factor in a number of eye diseases including age related macular degeneration and myopia. In this study, we undertook an epigenetic exploration of genes through analysis of methylation status in monozygotic (MZ) twins discordant for birth-weight.
From a total of 348 MZ twins who were examined as part of a larger study investigating eye diseases, those twin pairs in the top 5% for discordant birth-weight were selected for further study. DNA was available from twins at the time of adult age ascertainment. Genome-wide DNA methylation analysis on peripheral blood mononuclear cells using Illumina HumanMethylation27 BeadChips (Illumina 27K) was undertaken. This platform allows genome-wide single-CpG resolution DNA methylation measurements at 27,578 different CpG sites within 14,475 gene promoters.
Following quality control measures in the methylation analysis, data were available from 10 of the MZ birth-weight discordant twin pairs. While no one gene locus was significantly differentially methylated in all twin pairs, 21 loci were statistically significant differentially methylated in at least 4 of the 10 twin pairs, most notably the insulin receptor (INSR) gene.
Our data indicates a potential role for epigenetic modification by methylation in the control of birth weight. In particular the insulin receptor amongst other genes appears to be a key driver in this process. Further assessment of these genes in adults and their involvement as potential risk factors in eye disease is warranted.
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