Ann Pediatr Endocrinol Metab.  2020 Mar;25(1):31-37. 10.6065/apem.2020.25.1.31.

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

• Kang HR
• Hwang IT
• Yang S

• KMID: 2501034
• DOI: http://doi.org/10.6065/apem.2020.25.1.31

Abstract

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.

Keyword

Insulin-like growth factor binding protein 3; Polymorphism; Idiopathic short stature; Growth hormone

Figure

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  Fig. 1. Influence of -202 A/C IGFBP-3 genotype on first-year growth velocity SDS, IGF-1 SDS levels, and IGFBP-3 SDS levels in 69 children with ISS, before and after treatment. (A) ∆Height SDS/yr, (B) ∆IGF-1 SDS, (C) ∆IGFBP-3 SDS. IGFBP-3, insulin-like growth factor binding protein 3; SDS, standard deviation score; ISS, idiopathic short stature; IGF-1, insulin-like growth factor 1.

• 

  Fig. 2. Allelic frequency of -202 A/C IGFBP-3 polymorphisms after one year of rhGH treatment in children with ISS. The 69 patients were divided into 3 groups (n=23 per group) according to first-year growth velocity SDS (∆Height SDS/ yr): poor, <0.543; 0.543 to 0.812, moderate; and >0.812, good. IGFBP-3, insulin-like growth factor binding protein 3; rhGH, recombinant growth hormone; ISS, idiopathic short stature; SDS, standard deviation score.

Reference

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