Paternal transmission of the variant allele T for the RS1802710 single nucleotide polymorphism in DLK1 gene: relation with prenatal and postnatal growth

Abstract

Delta-like 1 homolog (DLK1) gene encodes a transmembrane protein containing epidermal growth factor-like repeats that promotes the induction of mesenchymal cells but prevents chondrocyte, preadipocytes and osteoblast maturation and differentiation. Rs1802710 polymorphism situated in the fifth exon of DLK1, shows a significant parent-of-origin effect reflecting the known silencing of the maternally inherited copy by imprinting. In humans, a more frequent paternal transmission of the paternal allele in the rs1802710 polymorphism of DLK1 on obese children has been noticed. We aimed to study the single nucleotide polymorphism (SNP) rs1802710 of the DLK1 gene and its effects on early life development. Due to the known imprinting effect surrounding the DLK1 locus, we wanted to analyze whether these changes were different depending on the parental origin of the transmitted rs1802710 variant T allele. Therefore, a longitudinal study has been done from the beginning of the pregnancy to the 12th month-old baby after birth. In order to be able to detect parent-of-origin effects, the whole trio family has been genotyped. Those families in which we were able to track the newborn rs1802710 T allele origin, were the ones selected for the complete analysis. Maternal anthropometric and metabolic variables, DLK1, MEG3 RTL1 and DIO3 gene expression, likewise newborn prenatal, perinatal and postnatal anthropometric variables were assessed to analyses differences when the the variant T allele was paternally or maternally transmitted to the newborn. DLK1 rs1802710 paternally expressed T allele was independently associated with low levels of maternal fatty acid synthase (β=0.415, p=0.024; model R2=0.142), generalized fetal growth rate increment (β = 0,268, p = 0,003; model R2 = 0.559), increased birth cranial perimeter-SDS (β=0.202, p=0.048; model R2=0.045) and with decreased ponderal index at 1st month of age (β=0.434, p=0.003; model R2=0.148). No significant differences were observed when the T allele was maternally received Those results highlight the paternal-origin effect that described in the DLK1 locus region