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

Xian-Hua Lin1,2, Dan-Dan Wu1,2, Ling Gao1,2

  • 1The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Oncotarget
|November 27, 2016
PubMed

Insights

Infants born large-for-gestational-age (LGA) exhibit higher cholesterol and insulin levels, increasing cardiometabolic disease risk. Epigenetic changes in umbilical cord blood may underlie these lipid dysfunctions, identifying potential biomarkers.

Area of Science:

  • Pediatric Endocrinology
  • Epigenetics
  • Cardiovascular Disease Risk

Background:

  • Infants born large-for-gestational-age (LGA) are at increased risk for developing cardiometabolic diseases.
  • The precise biological mechanisms linking LGA birth to later health issues remain largely undetermined.

Purpose of the Study:

  • To investigate the association between LGA birth and cardiometabolic risk factors in early childhood.
  • To explore genome-wide DNA methylation patterns in umbilical cord blood as potential mediators of LGA-associated metabolic dysfunction.

Main Methods:

  • A cohort study comparing 58 LGA children and 123 appropriate-for-gestational-age (AGA) children (aged 3-6 years).
  • Clinical measurements included anthropometrics, blood pressure, and metabolic assessments.
  • Genome-wide DNA methylation analysis was performed on umbilical cord blood samples from LGA and AGA newborns using the 450K BeadChip.

Main Results:

  • LGA children displayed significantly higher serum levels of total cholesterol (TC), LDL-c, insulin, and TC/HDL-c ratio compared to AGA children.
  • Birth weight positively correlated with serum TC, LDL-c, and TC/HDL-c ratio.
  • Genome-wide analysis identified 3459 methylation variable positions (MVPs), with 327 showing significant differences (≥7%) and mapping to 213 genes, including 16 linked to cardiovascular disease and 4 to hyperlipidemia.

Conclusions:

  • Excess birth weight (LGA) is associated with increased risk of lipid dysfunction in young children.
  • Epigenetic reprogramming of specific genes involved in cardiovascular disease may be a key mechanism.
  • The identified genes represent potential biomarkers for early detection of cardiometabolic disease risk.
Abstract

Keywords:
DNA methylationcardiometabolic risklarge-for-gestational-ageneonatepreschool children

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