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| Status |
Public on Jan 23, 2015 |
| Title |
In vivo investigations of the effect of short- and long-term recombinant growth hormone treatment on DNA-methylation in humans |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
Treatment with recombinant human growth hormone (rhGH) has been consistently reported to induce transcriptional changes in various human tissues including peripheral blood. For other hormones it has been shown that the induction of such transcriptional effects is conferred or at least accompanied by DNA-methylation changes. To analyse effects of short term rhGH treatment on the DNA-methylome we investigated a total of 24 patients at baseline and after 4-day rhGH stimulation. We performed array-based DNA-methylation profiling of paired peripheral blood mononuclear cell samples followed by targeted validation using bisulfite pyrosequencing. Unsupervised analysis of DNA-methylation in this short-term treated cohort revealed clustering according to individuals rather than treatment. Supervised analysis identified 239 CpGs as significantly differentially methylated between baseline and rhGH-stimulated samples (p<0.0001, unadjusted paired t-test), which nevertheless did not retain significance after adjustment for multiple testing. An individualised evaluation strategy led to the identification of 2350 CpG and 3 CpH sites showing methylation differences of at least 10% in more than 2 of the 24 analysed sample pairs. To investigate the long term effects of rhGH treatment on the DNA-methylome, we analysed peripheral blood cells from an independent cohort of 36 rhGH treated children born small for gestational age (SGA) as compared to 18 untreated controls. Median treatment interval was 33 months. In line with the groupwise comparison in the short-term treated cohort no differentially methylated targets reached the level of significance in the long-term treated cohort. We identified marked intra-individual responses of DNA-methylation to short-term rhGH treatment. These responses seem to be predominately associated with immunologic functions and show considerable inter-individual heterogeneity. The latter is likely the cause for the lack of a rhGH induced homogeneous DNA-methylation signature after short- and long-term treatment, which nevertheless is well in line with generally assumed safety of rhGH treatment.
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| Overall design |
Bisulfite converted DNA of PB from 36 SGA born children treated long-term with rhGH and 18 SGA born children with no rhGH treatment (controls) were hybridized to the Illumina Infinium HumanMethylation 450k Bead Chip.
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| Contributor(s) |
Kolarova J, Ammerpohl O, Gutwein J, Welzel M, Baus I, Riepe FG, Eggermann T, Caliebe A, Holterhus P, Siebert R, Bens S |
| Citation(s) |
25785847 |
| Submission date |
Apr 30, 2014 |
| Last update date |
Mar 22, 2019 |
| Contact name |
Susanne Bens |
| E-mail(s) |
sbens@medgen.uni-kiel.de
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| Organization name |
Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein
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| Department |
Institute of Human Genetics
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| Street address |
Arnold-Heller-Str.3 (Haus 10)
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| City |
Kiel |
| ZIP/Postal code |
D-24105 |
| Country |
Germany |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (54)
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| GSM1377074 |
DNA from PB S1, SGA, long-term rhGH treatment |
| GSM1377075 |
DNA from PB S2, SGA, long-term rhGH treatment |
| GSM1377076 |
DNA from PB S3, SGA, long-term rhGH treatment |
| GSM1377077 |
DNA from PB S4, SGA, long-term rhGH treatment |
| GSM1377078 |
DNA from PB S5, SGA, long-term rhGH treatment |
| GSM1377079 |
DNA from PB S6, SGA, long-term rhGH treatment |
| GSM1377080 |
DNA from PB S7, SGA, long-term rhGH treatment |
| GSM1377081 |
DNA from PB S8, SGA, long-term rhGH treatment |
| GSM1377082 |
DNA from PB S9, SGA, long-term rhGH treatment |
| GSM1377083 |
DNA from PB S10, SGA, long-term rhGH treatment |
| GSM1377084 |
DNA from PB S11, SGA, long-term rhGH treatment |
| GSM1377085 |
DNA from PB S12, SGA, long-term rhGH treatment |
| GSM1377086 |
DNA from PB S13, SGA, long-term rhGH treatment |
| GSM1377087 |
DNA from PB S14, SGA, long-term rhGH treatment |
| GSM1377088 |
DNA from PB S15, SGA, long-term rhGH treatment |
| GSM1377089 |
DNA from PB S16, SGA, long-term rhGH treatment |
| GSM1377090 |
DNA from PB S17, SGA, long-term rhGH treatment |
| GSM1377091 |
DNA from PB S18, SGA, long-term rhGH treatment |
| GSM1377092 |
DNA from PB S19, SGA, long-term rhGH treatment |
| GSM1377093 |
DNA from PB S20, SGA, long-term rhGH treatment |
| GSM1377094 |
DNA from PB S21, SGA, long-term rhGH treatment |
| GSM1377095 |
DNA from PB S22, SGA, long-term rhGH treatment |
| GSM1377096 |
DNA from PB S23, SGA, long-term rhGH treatment |
| GSM1377097 |
DNA from PB S24, SGA, long-term rhGH treatment |
| GSM1377098 |
DNA from PB S25, SGA, long-term rhGH treatment |
| GSM1377099 |
DNA from PB S26, SGA, long-term rhGH treatment |
| GSM1377100 |
DNA from PB S27, SGA, long-term rhGH treatment |
| GSM1377101 |
DNA from PB S28, SGA, long-term rhGH treatment |
| GSM1377102 |
DNA from PB S29, SGA, long-term rhGH treatment |
| GSM1377103 |
DNA from PB S30, SGA, long-term rhGH treatment |
| GSM1377104 |
DNA from PB S31, SGA, long-term rhGH treatment |
| GSM1377105 |
DNA from PB S32, SGA, long-term rhGH treatment |
| GSM1377106 |
DNA from PB S33, SGA, long-term rhGH treatment |
| GSM1377107 |
DNA from PB S34, SGA, long-term rhGH treatment |
| GSM1377108 |
DNA from PB S35, SGA, long-term rhGH treatment |
| GSM1377109 |
DNA from PB S36, SGA, long-term rhGH treatment |
| GSM1377110 |
DNA from PB S37, SGA, no rhGH treatment |
| GSM1377111 |
DNA from PB S38, SGA, no rhGH treatment |
| GSM1377112 |
DNA from PB S39, SGA, no rhGH treatment |
| GSM1377113 |
DNA from PB S40, SGA, no rhGH treatment |
| GSM1377114 |
DNA from PB S41, SGA, no rhGH treatment |
| GSM1377115 |
DNA from PB S42, SGA, no rhGH treatment |
| GSM1377116 |
DNA from PB S43, SGA, no rhGH treatment |
| GSM1377117 |
DNA from PB S44, SGA, no rhGH treatment |
| GSM1377118 |
DNA from PB S45, SGA, no rhGH treatment |
| GSM1377119 |
DNA from PB S46, SGA, no rhGH treatment |
| GSM1377120 |
DNA from PB S47, SGA, no rhGH treatment |
| GSM1377121 |
DNA from PB S48, SGA, no rhGH treatment |
| GSM1377122 |
DNA from PB S49, SGA, no rhGH treatment |
| GSM1377123 |
DNA from PB S50, SGA, no rhGH treatment |
| GSM1377124 |
DNA from PB S51, SGA, no rhGH treatment |
| GSM1377125 |
DNA from PB S52, SGA, no rhGH treatment |
| GSM1377126 |
DNA from PB S53, SGA, no rhGH treatment |
| GSM1377127 |
DNA from PB S54, SGA, no rhGH treatment |
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| This SubSeries is part of SuperSeries: |
| GSE57205 |
In vivo investigations of the effect of short- and long-term recombinant growth hormone treatment on DNA-methylation in humans |
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| Relations |
| BioProject |
PRJNA245905 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE57204_RAW.tar |
183.1 Mb |
(http)(custom) |
TAR |
| GSE57204_unmethylated_methylated_signals.txt.gz |
222.5 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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