ESPE2016 Free Communications Growth : Mechanisms (6 abstracts)
Preferential Transmission of the Paternal C Allele of the rs9373409 Polymorphism in plagl1 Gene as a Regulator of Fetal Growth and Maternal Metabolism
Anna Prats-Puig a, , Gemma Carreras-Badosa a, , Ferran Díaz-Roldán a, , Clive J Petry c , Clara Maldonado-Moreno d , Francis de Zegher e , Judit Bassols a, , Lourdes Ibáñez f , David B Dunger c & Abel Lopez-Bermejo a,
aGirona Institute for Biomedical Research, Girona, Spain; bEUSES University of Girona, Girona, Spain; cUniversity of Cambridge, Cambridge, UK; dDr. Josep Trueta Hospital, Girona, Spain; eUniversity of Leuven, Leuven, Spain; fHospital Sant Joan de Déu, Barcelona, Spain
Background: The phenotypic effects of single nucleotide polymorphisms (SNPs) may depend on their parental origin. PLAGL1 is an imprinted gene expressed from the paternal allele in placenta that is associated with fetal growth, transient neonatal diabetes mellitus and postnatal growth disorders. The mechanisms whereby PLAG1 regulates fetal growth are, however, unknown.
Objective and hypotheses: To study if the preferential paternal transmission of rs9373409 SNP alleles in PLAGL1 relates to fetal growth and maternal metabolism during pregnancy.
Method: We examined parent-to-offspring transmission of rs9373409 SNP alleles in PLAGL1 by means of real time PCR in leukocytes of 217 trios (apparently healthy mother-father-newborn trios; 651 samples). HOMA-IR, IGF-I and lipids were assessed in fasting serum samples of mothers during the second trimester of pregnancy. At birth, placentas and newborns were weighed and length and head circumference were measured in all infants. Finally, abdominal fat was measured by ultrasound one month after birth in the infants.
Results: The transmission of the paternal C allele of rs9373409 SNP in PLAGL1 gene (n=95 vs n=58 for the T allele and n=64 for heterozygotes) was associated with a higher birth weight (P=0.017), length (P=0.050) and head circumference (P=0.033) and increased abdominal fat (P=0.015) at one month of life. Mothers of infants receiving the C allele from the father exhibited a less favorable metabolic profile, showing increased HOMA-IR (P=0.023) and higher circulating IGF-I concentrations (P=0.003). All these associations remained significant after correcting for confounding variables such as: gestational age, gender, maternal age, maternal BMI and parity.
Conclusion: The transmission from the parent of the C allele of rs9373409 SNP in PLAGL1 may adversely affect maternal metabolism during gestation to promote fetal growth.
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