ESPE2024 Rapid Free Communications Fat, Metabolism and Obesity 1 (6 abstracts)
GRB10 methylation in umbilical cord associates postnatally with obesity in healthy children
Berta Mas-Parés 1 , Ariadna Gómez-Vilarrubla 1 , Maria Niubó-Pallàs 1 , Gemma Carreras-Badosa 1 , Anna Maroto 2 , José-María Martínez-Calcerrada 3 , Anna Prats-Puig 4 , Francis De Zegher 5 , Lourdes Ibáñez 6 , Judit Bassols 1 & Abel López-Bermejo 1,2,7
1Biomedical Research Institute of Girona, Girona, Spain. 2Josep Trueta Hospital, Girona, Spain. 3Legal Medicine Institute of Girona, Girona, Spain. 4Health and Sport university school (EUSES), Girona, Spain. 5University of Leuven, Leuven, Belgium. 6Sant Joan de Déu Hospital, Barcelona, Spain. 7University of Girona, Girona, Spain
Introduction and aims: The GRB10 gene codes for an adaptor protein that potentiates leptin signaling but inhibits IGF-I and insulin signaling. It is located on chromosome 7 and is imprinted in an isoform- and tissue-specific manner. The role of GRB10 in postnatal growth and obesity is not well understood, despite the fact that two imprinted disorders, Silver-Russell and Beckwith-Wiedmann syndromes, with distinctive postnatal growth abnormalities, have been related to abnormalities in GRB10 regulation and expression. We studied the methylation of an imprinted CG dinucleotide site annotating for GRB10 (chr7:50849285) in umbilical cord samples of healthy newborns and sought associations thereof with postnatal growth and obesity.
Subjects and Methods: The study population consisted of 97 pregnant women and their newborns who were followed from birth to 6 years of age, when anthropometry was performed. All mothers and newborns were healthy; all being term pregnancies and appropriate-weight-for-gestational-age infants. We assessed GRB10 methylation in umbilical cord samples using Epityper technology. Correlation analyses and multiple regression analyses were carried out.
Results: Umbilical cord methylation of GRB10 was positively correlated with obesity-related parameters in the offspring followed to 6 years of age. These findings remained statistically significant after adjusting for possible cofounding variables. Specifically, methylation of GRB10 correlated with weight-SDS (P = 0.004), BMI-SDS (P <0.001), waist-to-height ratio (P <0.001) and fat mass (P = 0.004) at 6 years of age. Additional associations were observed with weight-SDS increase from birth to 6 years of age (P = 0.003). Interestingly, when dividing the study population based on umbilical cord GRB10 methylation levels, we found that none of the infants with methylation levels below the median developed obesity at 6 years of age. In contrast, all the infants who had developed obesity at 6 years of age (BMI >2SDS) had methylation levels of GRB10 above the median.
Conclusion: Our findings suggest that GRB10 methylation in umbilical cord tissue associated postnatally with obesity in healthy children. Additionally, umbilical cord GRB10 methylation could have a predictive role in obesity development as early as 6 years of age.
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