Altered DNA methylation in neonates born large-for-gestational-age is associated with cardiometabolic risk in children
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Xian-hua Lin1,2,*, Dan-dan Wu1,2,*, Ling Gao1,2,*, Jun-yu Zhang1,2, Hai-tao Pan3, Hui Wang5, Cheng Li1,2, Ping Zhang1, Meng-xi Guo3, Yan-ting Wu1,2, Ya-jing Tan1,2, Li Jin1,2, Yu-qian Xiang1,2, Ju-xue Li1,2, Jian-zhong Sheng3,4, He-feng Huang1,2,3
1The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
2Institute of Embryo-Fetal Original Adult Disease, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
3The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, China
4Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, China
5Department of Obstetrics and Gynecology, Meihua Central Hospital, Shanghai, China
*These authors contributed equally to this work
He-feng Huang, email: [email protected]
Keywords: neonate, large-for-gestational-age, DNA methylation, preschool children, cardiometabolic risk
Received: July 26, 2016 Accepted: November 07, 2016 Published: November 18, 2016
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.
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