Developmental genes targeted for epigenetic variation between twin-twin transfusion syndrome children

Clinical Epigenetics

Francois Luks²  James F Padbury³  Charlotte M Boney¹  Debra Watson-Smith²  Devin C Koestler⁴  Carmen J Marsit⁴ 

[1] Department of Pediatrics, Rhode Island Hospital, Providence, RI USA;Program in Fetal Medicine, Warren Alpert Medical School at Brown University, Providence, RI USA;Department of Pediatrics, Women and Infants Hospital, Providence, RI, USA;Department of Community and Family Medicine, Section of Epidemiology and Biostatistics, Geisel Medical School at Dartmouth, Hanover, NH 03755, USA

关键词: Fetal;    Intrauterine environment;    DNA methylation;    Growth restriction;    Twin-twin transfusion syndrome;   

Others  :  790770
DOI  :  10.1186/1868-7083-5-18

 received in 2013-06-18, accepted in 2013-09-03,  发布年份 2013

【 摘 要 】

Background

Epigenetic mechanisms are thought to be critical in mediating the role of the intrauterine environment on lifelong health and disease. Twin-twin transfusion syndrome (TTTS) is a rare condition wherein fetuses share the placenta and develop vascular anastomoses, which allow blood to flow between the fetuses. The unequal flow results in reciprocal hypo- and hypervolemia in the affected twins, striking growth differences and physiologic adaptations in response to this significant stressor. The donor twin in the TTTS syndrome can be profoundly growth restricted and there is likely a nutritional imbalance between the twins. The consequences of TTTS on fetal programming are unknown. This condition can now be effectively treated through the use of fetal laparoscopic procedures, but the potential for lifelong morbidity related to this condition during development is apparent. As this condition and the resulting uteroplacental discordance can play a role in the epigenetic process, we sought to investigate the DNA methylation profiles of childhood survivors of TTTS (n = 14). We focused on differences in both global measures and genome-wide CpG specific DNA methylation between donor and recipient children in this pilot study in order to generate hypotheses for further research.

Results

We identified significant hypomethylation of the LINE1 repetitive element in the peripheral blood of donor children and subtle variation in the genome-wide profiles of CpG specific methylation most prominent at CpG sites which are targets for polycomb group repressive complexes.

Conclusions

These preliminary results suggest that coordinated epigenetic alterations result from the intrauterine environment experienced by infants with TTTS and may, at least in part, be responsible for downstream health conditions experienced by individuals surviving this condition.

【 授权许可】

   
2013 Marsit et al.; licensee BioMed Central Ltd.

【 图 表 】

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