ESPE Abstracts

Introduction: A global methylation array previously performed by our group in placental samples revealed a nominal association of a CpG site (CpGs) located at chr14:104552209 in the ASPG (Asparaginase) gene with childhood obesity. ASPG (Asparaginase) when used to treat haematologic neoplasms can cause liver steatosis. Asparaginase reduces asparagine blood levels, which is known to promote the development of metabolic syndrome and obesity in both children and adults. However, the potential role of ASPG methylation as a biomarker of childhood obesity remains unexplored.

Objectives: 1) To analyse the associations of placental ASPG methylation with obesity parameters in 6-year-old children. 2) To study the persistence of ASPG methylation over time by also analysing ASPG methylation in peripheral blood at 6 years of age. 3) To investigate the potential of ASPG methylation as a sustained biomarker for childhood obesity by assessing the association between ASPG methylation in peripheral blood samples at 6 years of age and obesity parameters.

Materials and Methods: The present study was performed in a population-based cohort of pregnant women and their newborns (n = 126, 59 girls and 67 boys) who were followed from birth to 6 years of age. Anthropometric and obesity parameters of the children [weight, height, BMI, subcutaneous and visceral fat (by ultrasound) and blood pressure] were assessed at 6 years of age. Children were classified into two groups according to their BMI at follow-up (BMI < 50^th centile and BMI > 50^th centile). The placental and peripheral blood ASPG methylation was assessed by pyrosequencing.

Results: Placental ASPG methylation was positively associated with changes in weight from birth to 6 years (P <0.01). ASPG methylation at birth (placenta) was highly correlated with ASPG methylation in peripheral blood at 6 years of age (P <0.0001). Peripheral blood ASPG methylation at 6 years of age was also positively associated with changes in weight from birth to 6 years (P <0.01). Notably, the aforementioned associations were heightened in children with higher BMI (BMI > 50^th centile). All the associations remained statistically significant in multivariate analyses.

Conclusion: Our findings reveal associations between ASPG methylation in placenta and obesity-related parameters in school-age children. ASPG methylation persists over time from birth (placenta) to school age (peripheral blood). Based on these results, we suggest a potential role of ASPG as an early and sustained epigenetic biomarker for identifying children at an increased risk of developing obesity.