ESPE Abstracts (2016) 86 FC14.4

ESPE2016 Free Communications Growth : Mechanisms (6 abstracts)

Preferential Paternal Transmission of the T Allele for the rs1802710 Polymorphism In Dlk1 Gene as a Pre- and Postnatal Growth Regulator

Anna Prats-Puig a, , Gemma Carreras-Badosa b, , Sílvia Xargay-Torrent b, , Clive J Petry c , Lara Redondo-Bautista d , Francis de Zegher e , Judit Bassols b, , Lourdes Ibáñez f , David B Dunger c & Abel Lopez-Bermejo b,

aEUSES University of Girona, Girona, Spain; bGirona Institute for Biomedical Research, Girona, Spain; cUniversity of Cambridge, Cambridge, UK; dDr. Josep Trueta Hospital, Girona, Spain; eUniversity of Leuven, Leuven, Belgium; fUniversity of Barcelona, Barcelona, Spain

Background: DLK1 or PREF1 is an imprinted gene highly expressed from the paternal allele in embryonic tissues and placenta. It has been recently implicated in adipose tissue expansion and diabetes development. The human rs1802710 polymorphism (SNP) in DLK1 gene has been associated with early-onset extreme obesity but its role determining growth is unknown.

Objective and hypotheses: To study the preferential paternal transmission of rs1802710 SNP T allele in DLK1 gene and its association with pre and postnatal growth as well as maternal metabolism during pregnancy.

Method: We genotyped the rs1802710 SNP in DLK1 gene in blood from 217 trios (apparently healthy mother-father-newborn trios; 651 samples) by means of real-time PCR. Fasting serum C-peptide and lipids were assessed in pregnant mothers during the second trimester. At birth, placentas and newborns were weighed and length and head circumference were measured in all infants. Additionally, fetal ultrasound measurements were recorded during pregnancy as well as weight and length of the infants during the first year of life.

Results: The T allele of rs1802710 SNP in DLK1 gene transmitted from the father (n=43 vs n=63 for the C allele and n=111 for heterozygotes) was related to a greater increase in fetal femur length (P=0.025) and both higher birth length (P=0.031) and head circumference (P=0.007). Moreover, these infants showed a greater weight gain at 4 (P=0.014), 6 (P=0.001) and 12 (P=0.023) months of life. Mothers, in turn, had higher C-peptide levels during pregnancy (P=0.03). These associations remained significant after correcting for confounding variables in multivariate analysis.

Conclusion: These results suggest that the transmission of the rs1802710 SNP in DLK1 gene may be a mechanism by which fathers can influence fetal and postnatal growth as well as maternal metabolism during pregnancy.

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