| Correlation analysis of clinical parameters with epigenetic modifications in the DUX4 promoter in FSHD. | |
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MedLine Citation:
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PMID: 22522912 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The aim of our study was to identify relationships between epigenetic parameters correlating with a relaxed chromatin state of the DUX4 promoter region and clinical severity as measured by a clinical severity score or muscle pathologic changes in D4Z4 contraction-dependent (FSHD1) and -independent (FSHD2) facioscapulohumeral muscular dystrophy patients. Twenty primary fibroblast (5 control, 10 FSHD1 and 5 FSHD2) and 26 primary myoblast (9 control, 12 FSHD1 and 5 FSHD2) cultures originating from patients with FSHD and controls were analyzed. Histone modification levels were determined by chromatin immunoprecipitation. We examined correlations between the chromatin compaction score (ChCS) defined by the H3K9me3:H3K4me2 ratio and an age corrected clinical severity score (CSS) or muscle pathology score (MPS). Possible relationships were investigated using linear regression analysis and significance was tested by Pearson's product-moment coefficient. We found a significant difference of the ChCS between controls and patients with FSHD1 and between controls and patients with FSHD2. Tissue specific differences in ChCS were also observed. We also found a near-significant relationship between ChCS and the age corrected CSS in fibroblasts but not in myoblasts. Surprisingly, we found a strong correlation between the MPS of the vastus lateralis and the CSS. Our results confirm the D4Z4 chromatin relaxation previously shown to be associated with FSHD in a small number of samples. A possible relationship between clinical and epigenetic parameters could be established in patient fibroblasts, but not in myoblasts. The strong correlation between the MPS of the vastus lateralis and the CSS suggests that this muscle can be used to study for surrogate markers of overall disease severity. |
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Authors:
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Judit Balog; Peter E Thijssen; Jessica C de Greef; Bharati Shah; Baziel G M van Engelen; Kyoko Yokomori; Stephen J Tapscott; Rabi Tawil; Silvère M van der Maarel |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-06-01 |
Journal Detail:
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Title: Epigenetics : official journal of the DNA Methylation Society Volume: 7 ISSN: 1559-2308 ISO Abbreviation: Epigenetics Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-07-03 Completed Date: 2012-11-09 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 101265293 Medline TA: Epigenetics Country: United States |
Other Details:
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Languages: eng Pagination: 579-84 Citation Subset: IM |
Affiliation:
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Department of Human Genetics; Leiden University Medical Center; Leiden, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Chromatin
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chemistry,
metabolism* Chromatin Immunoprecipitation Epigenesis, Genetic* Female Fibroblasts / metabolism Histones / chemistry, metabolism* Homeodomain Proteins / genetics*, metabolism Humans Male Muscular Dystrophy, Facioscapulohumeral / genetics*, metabolism, pathology Myoblasts / metabolism Promoter Regions, Genetic* Protein Processing, Post-Translational Regression Analysis Severity of Illness Index |
| Grant Support | |
ID/Acronym/Agency:
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P01NS069539/NS/NINDS NIH HHS; R01 AR045203/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chromatin; 0/DUX4 protein, human; 0/Histones; 0/Homeodomain Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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