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Oncotarget. 2016 Dec 27;7(52):86511-86521. doi: 10.18632/oncotarget.13442.

Altered DNA methylation in neonates born large-for-gestational-age is associated with cardiometabolic risk in children.

Lin XH1,2, Wu DD1,2, Gao L1,2, Zhang JY1,2, Pan HT3, Wang H4, Li C1,2, Zhang P1, Guo MX3, Wu YT1,2, Tan YJ1,2, Jin L1,2, Xiang YQ1,2, Li JX1,2, Sheng JZ3,5, Huang HF1,2,3.

Author information

1
The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
2
Institute of Embryo-Fetal Original Adult Disease, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
3
The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, China.
4
Department of Obstetrics and Gynecology, Meihua Central Hospital, Shanghai, China.
5
Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, China.

Abstract

BACKGROUND:

Infants being born Large-for-gestational-age (LGA) are prone to developing cardiometabolic disease. However, the underlying mechanisms remain unclear.

RESULTS:

Clinical 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 METHODS:

Fifty-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.

CONCLUSIONS:

Our 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.

KEYWORDS:

DNA methylation; cardiometabolic risk; large-for-gestational-age; neonate; preschool children

PMID:
27888796
PMCID:
PMC5349931
DOI:
10.18632/oncotarget.13442
[Indexed for MEDLINE]
Free PMC Article

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