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11p15 DNA-methylation analysis in monozygotic twins with discordant intrauterine development due to severe twin-to-twin transfusion syndrome

BACKGROUND: Prenatal growth restriction and low birth weight have been linked to long-term alterations of health, presumably via adaptive modifications of the epigenome. Recent studies indicate a plasticity of the 11p15 epigenotype in response to environmental changes during early stages of human de...

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Autores principales: Schreiner, Felix, Gohlke, Bettina, Stutte, Sonja, Bartmann, Peter, Hecher, Kurt, Oldenburg, Johannes, El-Maarri, Osman, Woelfle, Joachim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3986638/
https://www.ncbi.nlm.nih.gov/pubmed/24678997
http://dx.doi.org/10.1186/1868-7083-6-6
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author Schreiner, Felix
Gohlke, Bettina
Stutte, Sonja
Bartmann, Peter
Hecher, Kurt
Oldenburg, Johannes
El-Maarri, Osman
Woelfle, Joachim
author_facet Schreiner, Felix
Gohlke, Bettina
Stutte, Sonja
Bartmann, Peter
Hecher, Kurt
Oldenburg, Johannes
El-Maarri, Osman
Woelfle, Joachim
author_sort Schreiner, Felix
collection PubMed
description BACKGROUND: Prenatal growth restriction and low birth weight have been linked to long-term alterations of health, presumably via adaptive modifications of the epigenome. Recent studies indicate a plasticity of the 11p15 epigenotype in response to environmental changes during early stages of human development. STUDY DESIGN: We analyzed methylation levels at different 11p15 loci in 20 growth-discordant monozygotic twin pairs. Intrauterine development was discordant due to severe twin-to-twin transfusion syndrome (TTTS), which was treated by fetoscopic laser coagulation of communicating vessels before 25 weeks of gestation. Methylation levels at age 4 were determined in blood and buccal cell-derived DNA by the single nucleotide primer extension reaction ion pair reverse-phase high performance liquid chromatography (SNuPE IP RP HPLC) assay. Methylation at LINE-1 repeats was analyzed as an estimate of global methylation. RESULTS: In general, variance of locus-specific methylation levels appeared to be higher in buccal cell- as compared to blood cell-derived DNA samples. Paired analyses within the twin pairs revealed significant differences at only one CpG site (IGF2 dmr0 SN3 (blood), +1.9% in donors; P = 0.013). When plotting the twin pair-discordance in birth weight against the degree of discordance in site-specific methylation at age 4, only a few CpGs were found to interact (one CpG site each at IGF2dmr0 in blood/saliva DNA, one CpG at LINE-1 repeats in saliva DNA), with 26 to 36% of the intra-twin pair divergence at these sites explained by prenatal growth discordance. However, across the entire cohort of 40 children, site-specific methylation did not correlate with SD-scores for weight or length at birth. Insulin-like growth factor-II serum concentrations showed significant within-twin pair correlations at birth (R = 0.57) and at age 4 (R = 0.79), but did not differ between donors and recipients. They also did not correlate with the analyzed 11p15 methylation parameters. CONCLUSION: In a cohort of 20 growth-discordant monozygotic twin pairs, severe alteration in placental blood supply due to TTTS appears to leave only weak, if any, epigenetic marks at the analyzed CpG sites at 11p15.
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spelling pubmed-39866382014-04-16 11p15 DNA-methylation analysis in monozygotic twins with discordant intrauterine development due to severe twin-to-twin transfusion syndrome Schreiner, Felix Gohlke, Bettina Stutte, Sonja Bartmann, Peter Hecher, Kurt Oldenburg, Johannes El-Maarri, Osman Woelfle, Joachim Clin Epigenetics Research BACKGROUND: Prenatal growth restriction and low birth weight have been linked to long-term alterations of health, presumably via adaptive modifications of the epigenome. Recent studies indicate a plasticity of the 11p15 epigenotype in response to environmental changes during early stages of human development. STUDY DESIGN: We analyzed methylation levels at different 11p15 loci in 20 growth-discordant monozygotic twin pairs. Intrauterine development was discordant due to severe twin-to-twin transfusion syndrome (TTTS), which was treated by fetoscopic laser coagulation of communicating vessels before 25 weeks of gestation. Methylation levels at age 4 were determined in blood and buccal cell-derived DNA by the single nucleotide primer extension reaction ion pair reverse-phase high performance liquid chromatography (SNuPE IP RP HPLC) assay. Methylation at LINE-1 repeats was analyzed as an estimate of global methylation. RESULTS: In general, variance of locus-specific methylation levels appeared to be higher in buccal cell- as compared to blood cell-derived DNA samples. Paired analyses within the twin pairs revealed significant differences at only one CpG site (IGF2 dmr0 SN3 (blood), +1.9% in donors; P = 0.013). When plotting the twin pair-discordance in birth weight against the degree of discordance in site-specific methylation at age 4, only a few CpGs were found to interact (one CpG site each at IGF2dmr0 in blood/saliva DNA, one CpG at LINE-1 repeats in saliva DNA), with 26 to 36% of the intra-twin pair divergence at these sites explained by prenatal growth discordance. However, across the entire cohort of 40 children, site-specific methylation did not correlate with SD-scores for weight or length at birth. Insulin-like growth factor-II serum concentrations showed significant within-twin pair correlations at birth (R = 0.57) and at age 4 (R = 0.79), but did not differ between donors and recipients. They also did not correlate with the analyzed 11p15 methylation parameters. CONCLUSION: In a cohort of 20 growth-discordant monozygotic twin pairs, severe alteration in placental blood supply due to TTTS appears to leave only weak, if any, epigenetic marks at the analyzed CpG sites at 11p15. BioMed Central 2014-03-28 /pmc/articles/PMC3986638/ /pubmed/24678997 http://dx.doi.org/10.1186/1868-7083-6-6 Text en Copyright © 2014 Schreiner et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Schreiner, Felix
Gohlke, Bettina
Stutte, Sonja
Bartmann, Peter
Hecher, Kurt
Oldenburg, Johannes
El-Maarri, Osman
Woelfle, Joachim
11p15 DNA-methylation analysis in monozygotic twins with discordant intrauterine development due to severe twin-to-twin transfusion syndrome
title 11p15 DNA-methylation analysis in monozygotic twins with discordant intrauterine development due to severe twin-to-twin transfusion syndrome
title_full 11p15 DNA-methylation analysis in monozygotic twins with discordant intrauterine development due to severe twin-to-twin transfusion syndrome
title_fullStr 11p15 DNA-methylation analysis in monozygotic twins with discordant intrauterine development due to severe twin-to-twin transfusion syndrome
title_full_unstemmed 11p15 DNA-methylation analysis in monozygotic twins with discordant intrauterine development due to severe twin-to-twin transfusion syndrome
title_short 11p15 DNA-methylation analysis in monozygotic twins with discordant intrauterine development due to severe twin-to-twin transfusion syndrome
title_sort 11p15 dna-methylation analysis in monozygotic twins with discordant intrauterine development due to severe twin-to-twin transfusion syndrome
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3986638/
https://www.ncbi.nlm.nih.gov/pubmed/24678997
http://dx.doi.org/10.1186/1868-7083-6-6
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