Volume 2013 Supplement 1

7th Asia Pacific Paediatric Endocrine Society (APPES) Biennial Scientific Meeting

Open Access

Association of change on insulin-like growth factor (IGF)-i and IGF-binding protein 3 with genetic markers after a month of growth hormone (GH) therapy on Chinese children born with GH deficiency

  • Wei Wang1,
  • Shuixian Shen2,
  • Xiaoping Luo3,
  • Chunxiu Gong4,
  • Xuefan Gu5,
  • Yun Li6,
  • Minlian Minlian7,
  • Minlian Jin8 and
  • Bin Wu9
International Journal of Pediatric Endocrinology20132013(Suppl 1):P62

https://doi.org/10.1186/1687-9856-2013-S1-P62

Published: 3 October 2013

Aims

To identify genetic markers associated with changes in IGF-I and IGFBP3 standard deviation score (SDS) after 1 month of r-hGH treatment in Chinese GHD children either born Appropriate for Gestational Age (AGA) or Small for Gestational Age (SGA).

Methods

This phase IV open-label interventional study was performed on samples from 205 GHD children (175 subjects born AGA and 30 subjects SGA) of Chinese Han origin, recruited at 8 centers. All the subjects were given r-hGH for 4 weeks (0.033mg/kg/d).1536 SNPs were selected from 100 Candidate Genes involved in the GH-IGFI axes, growth plate and other short stature-related diseases. We genotyped Single nucleotide polymorphism (SNP) using Illumina GoldenGate™ Assays. Linear regression was used to identify single SNPs significantly associated with changes, from baseline to week 4, in serum IGF-I SDS and IGFBP3 SDS. Gestational age (GA) was also included in the model. The significance threshold was set as a corrected P-value<0.05. Multiple linear regressions with interaction effect were used to identify significantly associated genes with changes, from baseline to week 4, in serum IGF-I SDS and IGFBP3 SDS. The significance threshold was set as a corrected P-value<0.1.

Results

(1) 6/19 SNPs which correspond to 4/17 genes were significantly associated with IGF-I SDS change/IGFBP3 SDS change separately from baseline to Week 4 in all samples (AGA+SGA) with a corrected P-value<0.05. Among them, 3/10 SNPs showed significant interaction effects, suggesting that the pattern of SNPs associated with IGF-I SDS change/IGFBP3 SDS change was different between two groups.

(2) 14/14 genes which significantly associated with IGF-I SDS change/IGFBP3 SDS change at Week 4 were identified in all samples (AGA+SGA). Among them, 6/12 genes showed significant interaction effects, suggesting that IGF-I SDS change/IGFBP3 SDS change have different effect on these genes expression between two groups. We also found that 5 genes in common associated with both IGF-I SDS change and IGFBP-3 SDS change.

Conclusions

The results of our study demonstrate the genetic association between polymorphic variations of some candidate genes and serum IGF-I and IGFBP3 SDS changes after r-hGH therapy in children with GHD born SGA and AGA, suggesting that these genetic markers could be used into clinical practice in order to optimize efficacy, safety and cost of r-hGH therapy.

Authors’ Affiliations

(1)
Ruijin Hospital, Jiaotong University School Of Medicine
(2)
Children's Hospital of Fudan University
(3)
Tongji Hospital
(4)
Beijing Children's Hospital
(5)
Xinhua Hospital
(6)
Children's Hospital, Zhejiang University
(7)
First Affiliated Hospital, Sun Yat-sen University
(8)
Union Hospital
(9)
Merck Serono China

Copyright

© Wang et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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