Effect of -202 A/C IGFBP-3 polymorphisms on growth responses in children with idiopathic short stature.

Purpose: This study evaluated the -202 A/C insulin-like growth factor binding protein 3 (IGFBP-3) promoter polymorphism as a predictor of serum IGFBP-3 concentration and growth velocity after recombinant growth hormone (rhGH) therapy in patients with idiopathic short stature (ISS).

Methods: Genotyping and serial measurement of clinical parameters were performed in 69 children with a confirmed diagnosis of ISS. Restriction fragment length polymorphism analysis was performed to determine the genotype at the -202 IGFBP-3 locus. Serum insulin-like growth factor 1 (IGF-1) and IGFBP-3 levels were measured at baseline and after 1 year of rhGH treatment, as were height standard deviation score and growth velocity.

Results: The -202 A/C IGFBP-3 genotype comprised 69.6% AA, 24.6% AC, and 5.8% CC. One year of treatment did not produce a meaningful difference in IGF-1 or IGFBP-3 levels between children in the AA group and those with at least one copy of the C allele (AC/CC group). Comparing the 2 groups after one year also revealed no significant difference in growth velocity (ΔHeight: 9.061±1.612 cm/yr in the AA group, 9.421±1.864 in the AC/CC group, P=0.419).

Conclusion: rhGH treatment was effective and there were no significant differences in IGF-1, IGFBP-3, or growth velocity according to genotype. Thus, -202 IGFBP-3 genotype may not be a major factor affecting individual growth responses in Korean children with ISS.