ESPE Abstracts (2021) 94 P2-232

1Girona Biomedical Research Institute (IDIBGI), Salt, Spain; 2Dr. Josep Trueta Hospital, Girona, Spain; 3EUSES University of Girona, Salt, Spain; 4University of Leuven, Leuven, Belgium; 5Sant Joan de Déu Hospital, Barcelona, Spain


Introduction: It is known that excessive gestational weight gain can cause an adverse intrauterine environment and increase the risk of cardio-metabolic diseases in the offspring. Epigenetics could be one of the mechanisms involved in this regulation.

Objective: We aimed to study the DNA methylation profile of umbilical cord tissue that is associated with gestational weight gain (GWG), and its relationship with cardio-metabolic and anthropometric parameters in the offspring at 6 years of age.

Materials and methods: A methylation array was performed (Infinum®Methylation EPIC BeadChip) in umbilical cord tissue samples of 24 pregnant women with and without gestational obesity. The CpG dinucleotides whose methylation status was associated with GWG were validated in a cohort of 87 mother-newborn pairs by pyrosequencing and gene expression was studied by RT-PCR. A total of 61 newborns were followed up at 6 years of age and their cardio-metabolic and anthropometric parameters were assessed.

Results: The array identified 4451 CG dinucleotides differentially methylated and associated with GWG (all P < 0.05), of which 2778 presented gene annotation. Five genes with the greatest biological effects (Odds Ratio close to 1.1 or 0.91) were chosen for validation: SETD8, SLIT3, HOXC8, RPTOR and TMEm214. Children with higher methylation of SETD8 (lysine methyltransferase related to cell metabolism and proliferation) and lower methylation of SLIT3 (involved in cell proliferation and tissue development) showed a worse cardiometabolic profile at 6 years of age (higher BMI, fat mass, waist circumference and cIMT; all P < 0.05). The gene expression levels of SETD8 and SLIT3 were opposite to their methylation status and the children with lower and higher expression of SETD8 and SLIT3, respectively, presented differences in their cardiometabolic profile at 6 years old, in a way opposite to the methylation status. Finally, the methylation levels of HOXC8, RPTOR and TMEm214 also showed significant associations with different cardio-metabolic parameters, although no relation between methylation and gene expression was observed.

Conclusions: The methylation and gene expression of umbilical cord genes associate with GWG and the cardio-metabolic profile of the offspring at 6 years old. Epigenetic changes in the umbilical cord could explain, at least in part, the relationship between gestational obesity and cardio-metabolic risk in later life.

Volume 94

59th Annual ESPE (ESPE 2021 Online)

Online,
22 Sep 2021 - 26 Sep 2021

European Society for Paediatric Endocrinology 

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