The impact of imprinted genes on growth and cardiometabolic risk parameters in healthy children

ENG- Imprinted genes are expressed only from one parental allele, either from the mother or the father. They play fundamental roles in fetal and placental growth, as well as in neurobehavioral traits. These genes are implicated in several congenital syndromes known as imprinted disorders, which are lifelong conditions with a significant impact on health. Imprinted disorders share some clinical characteristics including pre- and/or postnatal growth retardation or overgrowth, hypo-or hyperglycemia, abnormal feeding behavior, and behavioral difficulties in childhood. Although alterations in imprinted genes related to these syndromes have been extensively studied, their role in prenatal and postnatal growth in the general population is less understood. In this context, the aim of this thesis was to analyse the association of imprinted genes in birth tissues with pre- and postnatal growth and cardiometabolic risk factors at six years of age, in children from the general population. To achieve this, we analysed the relationships between gene expression and DNA methylation of specific imprinted genes in placental and umbilical cord tissues and auxological parameters from a longitudinal cohort, with follow-up from birth to six years of age. We investigated three genes, known to have a role in two imprinted disorders (Prader-Willi and Silver-Russell). Notably, we found significant associations with all three genes and growth parameters, as well with obesity-related parameters. Specifically, both SNURF-SNRPN imprinted cluster and MEST demonstrated strong associations with auxological measurements from birth to six years of age, identifying them as potential predictors of growth trajectories during early infancy. While GRB10 was positively associated with obesity-related parameters, positioning it as a strong candidate biomarker for the development of childhood obesity. This thesis contributes valuable insights into the potential of these imprinted genes as biomarkers to predict growth patterns and obesity risk later in life – factors that are closely linked to increased disease risk in adulthood. Additionally, these genes offer opportunities for the development of new therapeutic targets