Mutation analysis of the growth factor genes PlGF, Flt1, IGF-I, and IGF-IR in intrauterine growth restriction with abnormal placental blood flow

J Matern Fetal Neonatal Med. 2010 Feb;23(2):142-7. doi: 10.3109/14767050903165198.

Abstract

Objective: The objective of our study was to investigate a possible role of pathogenic mutations in the growth factor genes insulin like growth factor I (IGF-I) and placental growth factor (PlGF) and their receptors IGF-IR and fms-like tyrosine kinase 1 (Flt1) in the pathogenesis of placental dysfunction.

Methods: We analyzed two patient groups with IUGR (intrauterine growth restriction), 18 mother-child pairs with absent or reversed enddiastolic flow (ARED) in the umbilical artery and 12 mother-child pairs with preserved enddiastolic flow (PED) in the presence of a bilateral abnormal uterine artery Doppler waveform (Notching). The control group comprised of 50 healthy mother-child pairs.

Results: Sequencing did not show a pathogenic mutation in any of the analyzed genes. However, we detected three novel polymorphisms in the IGF-IR gene. In addition, we identified one unknown polymorphism in exon 1 of the non-coding region of PlGF and 2 novel variants in exons 1 and 6 of Flt1.

Conclusion: In summary, our results do not provide evidence for a relevant role of pathogenic mutations in the genes IGF-I, IGF-IR, PlGF, and Flt1 in the etiology of IUGR with ARED or PED flow.

MeSH terms

  • Arteries / physiopathology
  • DNA Mutational Analysis
  • Diastole
  • Female
  • Fetal Growth Retardation / genetics*
  • Fetal Growth Retardation / physiopathology
  • Humans
  • Insulin-Like Growth Factor I / genetics*
  • Placenta / blood supply*
  • Placenta Growth Factor
  • Polymorphism, Genetic
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single-Stranded Conformational
  • Pregnancy
  • Pregnancy Proteins / genetics*
  • Receptor, IGF Type 1 / genetics*
  • Umbilical Arteries / physiopathology
  • Vascular Endothelial Growth Factor Receptor-1 / genetics*

Substances

  • PGF protein, human
  • Pregnancy Proteins
  • Placenta Growth Factor
  • Insulin-Like Growth Factor I
  • FLT1 protein, human
  • Receptor, IGF Type 1
  • Vascular Endothelial Growth Factor Receptor-1