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

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.