Study of the regulation of the IGFBP3 gene expression in short children born small for gestational age

Approximately 6% of newborns at term are small for gestational age (SGA) (birth weight and/or length less than -2SD from the mean) and 10% of them does not show the catch up growth within the 2° year of postnatal life. Alterations of the genes involved in the signal transduction pathways of growth hormone (GH) and insulin-like growth factors (IGFs), especially IGF-I, may play a key role in these children. However, up to now, only exceptionally mutations or deletions of IGF-related genes have been reported in SGA children. Therefore, the attention has been focused on the promoter polymorphisms of IGF-related genes and on the functional study of the promoter regions of genes involved in these pathways, looking for new regulatory elements and factors that might alter gene expression. Recently, it has been shown that the polymorphism -202 A/C in the IGF-binding protein 3 (IGFBP3) gene's promoter region causes the alteration of its transcriptional activity (1). IGFBP3, the most abundant circulating IGFBP, transports more than 75% of serum IGFs, extends IGFs' half-life, and modulates their biological effects. In addition, IGFBP3 also has IGF-independent effects including cell growth inhibition and induction of apoptosis.