ESPE Abstracts (2015) 84 P-2-483

Hypermethylation at the Imprinted C19mc Microrna Cluster: A New Link between Maternal Metabolism and Infant's Growth

Anna Prats-Puiga,c, Gemma Carreras-Badosaa,b, Judit Bassolsa,b, Michael Girardotf, Empar Carrionb, Radu Gehmisa,b, Francis de Zegherd, Lourdes Ibáñeze, Robert Feilf & Abel López-Bermejoa,b

aGirona Institute for Biomedical Research, Girona, Spain; bDr.JosepTrueta Hospital, Girona, Spain; cEUSES University School, Girona, Spain; dUniversity of Leuven, Leuven, Belgium; eHospital Sant Joan de Déu, Barcelona, Spain; fInstitut de Génétique Moléculaire de Montpellier, Montpellier, France

Background: Maternal obesity can have long-term consequences for the offspring’s health, including increased risk of type-2 diabetes and cardiovascular disease. The C19MC imprinted locus on chromosome 19q13.4 comprises a cluster of 46 microRNAs, which are usually expressed only in the placenta and from the paternal allele exclusively. Besides its role favouring trophoblast migration, the C19MC locus is deregulated in several human cancers. It is unknown whether the degree of DNA methylation at the C19MC locus could be linked to maternal metabolism and infant’s growth.

Objective and hypotheses: To determine the association between DNA methylation at C19MC and maternal weight, blood pressure and post-load glucose, and with the infant’s weight and length.

Method: The degree of DNA methylation at 3 CpG dinucleotides in the C19MC promoter was studied by means of pyrosequencing in placentas from 79 healthy pregnancies. The studied chromosomal location within the cluster was chr19:54,151,133-54,151,183. A glucose-challenge test was performed between 24 and 28 weeks of gestation. Maternal weight and blood pressure data were also collected prior to birth. At delivery, placentas were collected and weighed, and the weight and length of the newborns were measured (gestational age 39±1 weeks; birth weight z-score 0.31±0.89).

Results: Increased placental methylation of the C19MC locus was associated with maternal obesity (P=0.016). Furthermore, higher levels of methylation were also associated with higher maternal systolic blood pressure (r=0.430; P=0.001) and post-load glucose levels (r=0.264; P=0.035). Higher placental levels of methylation were also associated with increased infant’s growth, showing positive associations with weight z-score (P=0.267; r=0.026) and height z-score (r=0.272; P=0.024) at birth. All these associations remained significant after adjusting for confounding variables.

Conclusion: This study shows for the first time that aberrant hypermethylation at the C19MC locus provides a link between a poorer maternal metabolic phenotype and increased growth of the offspring.

Funding information: This study was supported by a grant from the Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III (ISCIII), Madrid, Spain (PI13/01257), project co-financed by FEDER.