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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 PBMC from 24 patients before and after 4 days of rhGH treatment were hybridized to the Illumina Infinium HumanMethylation 450k BeadChip.
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| Contributor(s) |
Kolarova J, Ammerpohl O, Gutwein J, Welzel M, Baus I, Riepe FG, Eggermann T, Caliebe A, Holterhus PM, Siebert R, Bens S |
| Citation(s) |
25785847 |
| Submission date |
Apr 25, 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 (48)
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| GSM1375361 |
DNA from PBMC P4, baseline |
| GSM1375362 |
DNA from PBMC P7, baseline |
| GSM1375363 |
DNA from PBMC P8, baseline |
| GSM1375364 |
DNA from PBMC P9, baseline |
| GSM1375365 |
DNA from PBMC P10, baseline |
| GSM1375366 |
DNA from PBMC P11, baseline |
| GSM1375367 |
DNA from PBMC P12, baseline |
| GSM1375368 |
DNA from PBMC P13, baseline |
| GSM1375369 |
DNA from PBMC P14, baseline |
| GSM1375370 |
DNA from PBMC P15, baseline |
| GSM1375371 |
DNA from PBMC P16, baseline |
| GSM1375372 |
DNA from PBMC P17, baseline |
| GSM1375373 |
DNA from PBMC P18, baseline |
| GSM1375374 |
DNA from PBMC P19, baseline |
| GSM1375375 |
DNA from PBMC P20, baseline |
| GSM1375376 |
DNA from PBMC P21, baseline |
| GSM1375377 |
DNA from PBMC P22, baseline |
| GSM1375378 |
DNA from PBMC P23, baseline |
| GSM1375379 |
DNA from PBMC P24, baseline |
| GSM1375380 |
DNA from PBMC P25, baseline |
| GSM1375381 |
DNA from PBMC P26, baseline |
| GSM1375382 |
DNA from PBMC P1, 4 days rhGH treatment |
| GSM1375383 |
DNA from PBMC P2, 4 days rhGH treatment |
| GSM1375384 |
DNA from PBMC P3, 4 days rhGH treatment |
| GSM1375385 |
DNA from PBMC P4, 4 days rhGH treatment |
| GSM1375386 |
DNA from PBMC P7, 4 days rhGH treatment |
| GSM1375387 |
DNA from PBMC P8, 4 days rhGH treatment |
| GSM1375388 |
DNA from PBMC P9, 4 days rhGH treatment |
| GSM1375389 |
DNA from PBMC P10, 4 days rhGH treatment |
| GSM1375390 |
DNA from PBMC P11, 4 days rhGH treatment |
| GSM1375391 |
DNA from PBMC P12, 4 days rhGH treatment |
| GSM1375392 |
DNA from PBMC P13, 4 days rhGH treatment |
| GSM1375393 |
DNA from PBMC P14, 4 days rhGH treatment |
| GSM1375394 |
DNA from PBMC P15, 4 days rhGH treatment |
| GSM1375395 |
DNA from PBMC P16, 4 days rhGH treatment |
| GSM1375396 |
DNA from PBMC P17, 4 days rhGH treatment |
| GSM1375397 |
DNA from PBMC P18, 4 days rhGH treatment |
| GSM1375398 |
DNA from PBMC P19, 4 days rhGH treatment |
| GSM1375399 |
DNA from PBMC P20, 4 days rhGH treatment |
| GSM1375400 |
DNA from PBMC P21, 4 days rhGH treatment |
| GSM1375401 |
DNA from PBMC P22, 4 days rhGH treatment |
| GSM1375402 |
DNA from PBMC P23, 4 days rhGH treatment |
| GSM1375403 |
DNA from PBMC P24, 4 days rhGH treatment |
| GSM1375404 |
DNA from PBMC P25, 4 days rhGH treatment |
| GSM1375405 |
DNA from PBMC P26, 4 days 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 |
PRJNA245442 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE57107_RAW.tar |
183.1 Mb |
(http)(custom) |
TAR |
| GSE57107_unmethylated_methylated_signals.txt.gz |
198.2 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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