Abstract
BackgroundInfants being born Large-for-gestational-age (LGA) are prone to developing cardiometabolic disease. However, the underlying mechanisms remain unclear.ResultsClinical investigation showed that children born LGA had significantly higher serum level of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and insulin, ratio of TC/high-density lipoprotein-cholesterol (HDL-c) compared to children born appropriate for gestational age (AGA). Birth weight (BW) was positively correlated to TC, LDL-c, and the ratio of TC/HDL in serum. Genome-wide DNA methylation analyzed in umbilical cord blood of controls and macrosomia cases. We identified 3459 methylation variable positions (MVPs) achieving genome-wide significance (adjusted P-value < 0.05) with methylation differences of ≥ 5%. A total of 327 MVPs were filtered by methylation differences of ≥ 7% located within an island, which mapped to 213 genes. Function analysis using Ingenuity Pathway Analysis showed 16 genes enriched in “cardiovascular disease”. Four genes included contributed to hyperlipidemia.Materials And MethodsFifty-eight children aged 3–6 years born LGA and 123 subjects born AGA were enrolled. Anthropometric parameters and blood pressure (BP) were measured, and metabolic assessment was performed in all subjects. Genome-wide DNA methylation in umbilical blood was assayed by the 450K BeadChip in six AGA and six macrosomia newborns.ConclusionsOur data indicate that excess birth weight may increase the risk of lipid dysfunction in children aged 3–6 years. It might through reprogramming a group of genes correlated to cardiovascular disease. The genes identified in this study might be potential biomarker for cardiometabolic disease.
Highlights
Prenatal and early postnatal origins of cardiometabolic disease have been extensive studied in the past a few years
Clinical investigation showed that children born LGA had significantly higher serum level of total cholesterol (TC), low-density lipoproteincholesterol (LDL-c), and insulin, ratio of TC/high-density lipoprotein-cholesterol (HDL-c) compared to children born appropriate for gestational age (AGA)
A total of 327 methylation variable positions (MVPs) were filtered by methylation differences of ≥ 7% located within an island, which mapped to 213 genes
Summary
Prenatal and early postnatal origins of cardiometabolic disease have been extensive studied in the past a few years. Infants being born LGA are prone to developing obesity, diabetes, and hypertension during childhood and later in life [2, 3]. Being born LGA to mothers with or without gestational diabetes mellitus (GDM) and obesity is associated with diverse effects on cardiometabolic risk factors at prepuberty [4,5,6]. Other studies have shown that high birth weight and rapid weight gain in childhood are associated with cardiometabolic risk later in life [7,8,9,10]. Infants being born Large-for-gestational-age (LGA) are prone to developing cardiometabolic disease.
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