Novel promoter polymorphism in insulinlike growth factor-binding protein-3: correlation with serum levels and interaction with known regulators

Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) is a major determinant of circulating levels of the IGFs and is clinically useful for the evaluation of GH deficiency and for predicting the response to GH treatment. Recent studies provide evidence that the circulating level of IGFBP-3 is inversely related to the risk of several common cancers, and that antiproliferative agents such as anties-trogens and retinoids act in part by up-regulating IGFBP-3 gene (IGFBP3) expression. Although approximately 50 % of the substantial interindividual variability in circulating IGFBP-3 levels is known to have a genetic basis, the specific loci involved are unknown. Direct sequencing of genomic DNA specimens from a multiethnic population identified several single nucleotide polymorphisms in the promoter region of IGFBP3. For the most common single nucleotide polymorphism (nucleotide 2202) found to be in Hardy-Weinberg equi