Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Schreiner F

PROVIDER: S-EPMC3986638 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Publications

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

Schreiner Felix F Gohlke Bettina B Stutte Sonja S Bartmann Peter P Hecher Kurt K Oldenburg Johannes J El-Maarri Osman O Woelfle Joachim J

Clinical epigenetics 20140328 1

<h4>Background</h4>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.<h4>Study design</h4>We analyzed methylation levels at different 11p15 loci in 20 growth-discordant monozygotic twin pairs. Intrauterine development was discordant due to severe twin- ...[more]

PMID: 24678997

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Project description:BackgroundRheumatoid arthritis is a common autoimmune disorder influenced by both genetic and environmental factors. Epigenome-wide association studies can identify environmentally mediated epigenetic changes such as altered DNA methylation, which may also be influenced by genetic factors. To investigate possible contributions of DNA methylation to the aetiology of rheumatoid arthritis with minimum confounding genetic heterogeneity, we investigated genome-wide DNA methylation in disease-discordant monozygotic twin pairs.MethodsGenome-wide DNA methylation was assessed in 79 monozygotic twin pairs discordant for rheumatoid arthritis using the HumanMethylation450 BeadChip array (Illumina). Discordant twins were tested for both differential DNA methylation and methylation variability between rheumatoid arthritis and healthy twins. The methylation variability signature was then compared with methylation variants from studies of other autoimmune diseases and with an independent healthy population.ResultsWe have identified a differentially variable DNA methylation signature that suggests multiple stress response pathways may be involved in the aetiology of the disease. This methylation variability signature also highlighted potential epigenetic disruption of multiple RUNX3 transcription factor binding sites as being associated with disease development. Comparison with previously performed epigenome-wide association studies of rheumatoid arthritis and type 1 diabetes identified shared pathways for autoimmune disorders, suggesting that epigenetics plays a role in autoimmunity and offering the possibility of identifying new targets for intervention.ConclusionsThrough genome-wide analysis of DNA methylation in disease-discordant monozygotic twins, we have identified a differentially variable DNA methylation signature, in the absence of differential methylation in rheumatoid arthritis. This finding supports the importance of epigenetic variability as an emerging component in autoimmune disorders.

Dataset Information

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

Background

Study design

Results

Conclusion

Publications

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

Similar Datasets

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