Genome-wide peripheral blood leukocyte DNA methylation microarrays identified a single association with inflammatory bowel diseases.

Genome-wide peripheral blood leukocyte DNA methylation microarrays identified a single association with inflammatory bowel diseases.
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DOI:
10.1002/ibd.22956
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发表时间:
2012-12
影响因子:
4.9
通讯作者:
Kellermayer, Richard
Kellermayer, Richard
中科院分区:
医学2区
文献类型:
--
作者:
Harris, R. Alan;Nagy-Szakal, Dorottya;Pedersen, Natalia;Opekun, Antone;Bronsky, Jiri;Munkholm, Pia;Jespersgaard, Cathrine;Andersen, PaalSkytt;Melegh, Bela;Ferry, George;Jess, Tine;Kellermayer, Richard

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Crohn disease (CD) and ulcerative colitis (UC) are common forms of inflammatory bowel diseases (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 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.
DOI: 10.1002/ibd.21352
发表时间: 2011-01
影响因子: 4.9
作者:
Gonsky, Rivkah;Deem, Richard L.;Landers, Carol J.;Derkowski, Carrie A.;Berel, Dror;McGovern, Dermot P. B.;Targan, Stephan R.
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发表时间: 2010-04-01
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影响因子: 3.1
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