IGF1 gene is epigenetically activated in preterm infants with intrauterine growth restriction

Clin Epigenetics. 2020 Jul 16;12(1):108. doi: 10.1186/s13148-020-00901-w.


Background: IGF1 is a key molecule in the regulation of growth and metabolism. Low IGF1 secretion is known to cause growth restriction in childhood, as well as deregulated lipid metabolism, cardiovascular disease, and diabetes in adulthood. The IGF1 gene P2 promoter is highly methylated, resulting in low secretion of IGF1 in small infants and children. However, it is unknown when this methylation occurs. The aim of study was to clarify the point when this epigenetic program occurs during intrauterine development. We analyzed 56 preterm infants born before 32 weeks of gestation, including 19 intrauterine growth restriction (IUGR) infants whose birth weights were lower than - 2SD calculated by the Japanese datasets. We extracted genomic DNA from whole blood at birth; methylation of the six CpG sites in the IGF1 P2 promoter was analyzed by the bisulfite amplicon method using the MiSeq platform.

Results: In contrast to term infants and children, the methylation of all six CpG sites positively correlated with body weight and body length at birth. IGF1 P2 promoter methylation levels were significantly reduced in all six CpG sites in infants with IUGR.

Conclusions: These findings indicated that the IGF1 gene is epigenetically activated before 32 weeks of gestation in infants with IUGR and that the activated gene may become suppressed after this time point. This study may provide new insights to prevent the onset of adult diseases and to aid in nutritional management for preterm birth infants in neonatal intensive care units.

Keywords: Epigenetics; IGF1; IUGR; Intrauterine growth restriction; Methylation; Newborn infant; P2 promoter; Preterm.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cardiovascular Diseases / genetics
  • Case-Control Studies
  • Child
  • CpG Islands / genetics
  • DNA Methylation / genetics
  • Diabetes Mellitus / genetics
  • Epigenomics / methods*
  • Female
  • Fetal Growth Retardation / genetics*
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Infant, Small for Gestational Age / blood
  • Insulin-Like Growth Factor I / genetics*
  • Intensive Care Units, Neonatal / standards
  • Lipid Metabolism Disorders / genetics
  • Nutrition Therapy / methods
  • Pregnancy
  • Premature Birth / genetics
  • Promoter Regions, Genetic


  • IGF1 protein, human
  • Insulin-Like Growth Factor I