These authors contributed equally.
Genome-wide peripheral blood leukocyte DNA methylation microarrays identified a single association with inflammatory bowel diseases†
Article first published online: 29 MAR 2012
Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 18, Issue 12, pages 2334–2341, December 2012
How to Cite
Harris, R. A., Nagy-Szakal, D., Pedersen, N., Opekun, A., Bronsky, J., Munkholm, P., Jespersgaard, C., Andersen, P., Melegh, B., Ferry, G., Jess, T. and Kellermayer, R. (2012), Genome-wide peripheral blood leukocyte DNA methylation microarrays identified a single association with inflammatory bowel diseases. Inflamm Bowel Dis, 18: 2334–2341. doi: 10.1002/ibd.22956
R.K. was supported in part by the Broad Medical Research Program, the Broad Foundation (IBD-0252); the Crohn's and Colitis Foundation of America-Children's Digestive Health and Nutrition Foundation/North American Society of Pediatric Gastroenterology Hepatology and Nutrition (CCFA Ref. No. 2426); the Child Health Research Career Development Agency of the Baylor College of Medicine (NIH Grant No. 5K12 HD041648); and a Public Health Service grant DK56338, funding the Texas Medical Center Digestive Diseases Center.
- Issue published online: 15 NOV 2012
- Article first published online: 29 MAR 2012
- Manuscript Accepted: 22 FEB 2012
- Manuscript Received: 13 FEB 2012
- inflammatory bowel disease;
- DNA methylation;
- peripheral blood;
Crohn's disease (CD) and ulcerative colitis (UC) are common forms of inflammatory bowel disease (IBD). Monozygotic (MZ) twin discordance rates and epidemiologic data implicate that environmental changes and epigenetic factors may play a pathogenic role in IBD. DNA methylation (the methylation of cytosines within CpG dinucleotides) is an epigenetic modification, which can respond to environmental influences. We investigated whether DNA methylation might be connected with IBD in peripheral blood leukocyte (PBL) DNA by utilizing genome-wide microarrays.
Two different high-throughput microarray-based methods for genome-wide DNA methylation analysis were employed. First, DNA isolated from MZ twin pairs concordant (CD: 4; UC: 3) and discordant (CD: 4; UC: 7) for IBD was interrogated by a custom-made methylation-specific amplification microarray (MSAM). Second, the recently developed Illumina Infinium HumanMethylation450 BeadChip arrays were used on 48 samples of PBL DNA from discordant MZ twin pairs (CD: 3; UC: 3) and treatment-naive pediatric cases of IBD (CD: 14; UC: 8), as well as controls (n = 14). The microarrays were validated with bisulfite pyrosequencing.
The MSAMs did not yield significant IBD associations. The Methylation BeadChip approach identified a single DNA methylation association of IBD at TEPP (testis, prostate and placenta-expressed protein) when DNA isolated selectively from peripheral blood mononuclear cells was analyzed (8.6% increase in methylation between CD and control, FDR = 0.0065).
Microarray interrogation of IBD-dependent DNA methylation from PBLs appears to have limited ability to detect significant disease associations. More detailed and/or selective approaches may be useful for the elucidation of connections between the DNA methylome and IBD in the future. (Inflamm Bowel Dis 2012;)