NDLI: Genome-wide analysis of DNA methylation in subjects with type 1 diabetes identifies epigenetic modifications associated with proliferative diabetic retinopathy

Content Provider	Springer Nature : BioMed Central
Author	Agardh, Elisabet Lundstig, Annika Perfilyev, Alexander Volkov, Petr Freiburghaus, Tove Lindholm, Eero Rönn, Tina Agardh, Carl-David Ling, Charlotte
Abstract	Background Epigenetic variation has been linked to several human diseases. Proliferative diabetic retinopathy (PDR) is a major cause of vision loss in subjects with diabetes. However, studies examining the association between PDR and the genome-wide DNA methylation pattern are lacking. Our aim was to identify epigenetic modifications that associate with and predict PDR in subjects with type 1 diabetes (T1D). Methods DNA methylation was analyzed genome-wide in 485,577 sites in blood from cases with PDR (n = 28), controls (n = 30), and in a prospective cohort (n = 7). False discovery rate analysis was used to correct the data for multiple testing. Study participants with T1D diagnosed before 30 years of age and insulin treatment within 1 year from diagnosis were selected based on 1) subjects classified as having PDR (cases) and 2) subjects with T1D who had had diabetes for at least 10 years when blood DNA was sampled and classified as having no/mild diabetic retinopathy also after an 8.7-year follow-up (controls). DNA methylation was also analyzed in a prospective cohort including seven subjects with T1D who had no/mild diabetic retinopathy when blood samples were taken, but who developed PDR within 6.3 years (converters). The retinopathy level was classified by fundus photography. Results We identified differential DNA methylation of 349 CpG sites representing 233 unique genes including TNF, CHI3L1 (also known as YKL-40), CHN2, GIPR, GLRA1, GPX1, AHRR, and BCOR in cases with PDR compared with controls. The majority of these sites (79 %) showed decreased DNA methylation in cases with PDR. The Natural Killer cell-mediated cytotoxicity pathway was found to be significantly (P = 0.006) enriched among differentially methylated genes in cases with PDR. We also identified differential DNA methylation of 28 CpG sites representing 17 genes (e.g. AHRR, GIPR, GLRA1, and BCOR) with P <0.05 in the prospective cohort, which is more than expected by chance (P = 0.0096). Conclusions Subjects with T1D and PDR exhibit altered DNA methylation patterns in blood. Some of these epigenetic changes may predict the development of PDR, suggesting that DNA methylation may be used as a prospective marker of PDR.
Related Links	https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-015-0421-5.pdf
Ending Page	9
Page Count	9
Starting Page	1
File Format	HTM / HTML
ISSN	17417015
DOI	10.1186/s12916-015-0421-5
Journal	BMC Medicine
Issue Number	1
Volume Number	13
Language	English
Publisher	BioMed Central
Publisher Date	2015-08-06
Access Restriction	Open
Subject Keyword	Medicine Public Health Biomedicine Diabetic complication DNA methylation Epigenetics Inflammation Prediction Proliferative retinopathy Prospective Type 1 diabetes Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Medicine
Journal Impact Factor	7.1/2023
5-Year Journal Impact Factor	8.8/2023

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