title: Altered DNA methylation in neonates born large-for-gestational-age is associated with cardiometabolic risk in children.
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.
  
  
  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.
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Institute of Embryo-Fetal Original Adult Disease, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Xian-Hua
authors.initials: XH
authors.lastname: Lin
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Institute of Embryo-Fetal Original Adult Disease, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Wu
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Institute of Embryo-Fetal Original Adult Disease, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Institute of Embryo-Fetal Original Adult Disease, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Jun-Yu
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, China.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Pan
authors.affiliation: Department of Obstetrics and Gynecology, Meihua Central Hospital, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Institute of Embryo-Fetal Original Adult Disease, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Li
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, China.
authors.forename: Meng-Xi
authors.initials: MX
authors.lastname: Guo
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Institute of Embryo-Fetal Original Adult Disease, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Yan-Ting
authors.initials: YT
authors.lastname: Wu
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Institute of Embryo-Fetal Original Adult Disease, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Tan
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Institute of Embryo-Fetal Original Adult Disease, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Institute of Embryo-Fetal Original Adult Disease, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Yu-Qian
authors.initials: YQ
authors.lastname: Xiang
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Institute of Embryo-Fetal Original Adult Disease, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Ju-Xue
authors.initials: JX
authors.lastname: Li
authors.affiliation: The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, China.|Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Sheng
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Institute of Embryo-Fetal Original Adult Disease, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.|The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, China.
authors.forename: He-Feng
authors.initials: HF
authors.lastname: Huang
mesh_terms: D001724:Birth Weight; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D005260:Female; D005865:Gestational Age; D006801:Humans; D006949:Hyperlipidemias / Q000209:etiology*; D007231:Infant, Newborn; D008297:Male; D012306:Risk
keywords: DNA methylation; cardiometabolic risk; large-for-gestational-age; neonate; preschool children