Ann Pediatr Endocrinol Metab.  2017 Mar;22(1):36-42. 10.6065/apem.2017.22.1.36.

Influence of The -202 A/C insulin-like growth factor-binding protein-3 promoter polymorphism on individual variation in height in Korean girls

Affiliations
  • 1Department of Pediatrics, Hallym University College of Medicine, Seoul, Korea. drsyang@hallym.or.kr

Abstract

PURPOSE
The most common single nucleotide polymorphism in the IGFBP3 promoter region occurs at position -202. This polymorphic variation occurs frequently and may influence growth hormone responsiveness and somatic growth. However, the effects of IGFBP3 promoter polymorphism on growth in children are unknown.
METHODS
Restriction fragment length polymorphism-based genotyping of the -202 single nucleotide polymorphism was performed in 146 Korean girls aged between 15 and 16 years, who were selected randomly from the Seoul School Health Promotion Center. The participants were divided into 3 groups (tall, medium, and short) according to the height percentile established from normal reference values for Korean children. The serum levels of insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) were then compared according to genotype.
RESULTS
The genotype distribution in the participants was 79 AA (54.1%), 60 AC (41.1%), and 7 CC (4.8%). The C allele frequency at the -202 IGFBP3 position was 25.4% in this group. The mean serum IGFBP-3 concentration in girls with the AA genotype was higher than that in girls with the AC genotype in the medium (P=0.047) and short (P=0.035) groups, respectively. There was no difference in the IGF-I to IGFBP-3 molar ratio between the AA and AC genotype groups (P=0.161).
CONCLUSION
In conclusion, the -202 polymorphism in the IGFBP3 promoter region is assumed to affect the serum concentration of IGFBP-3 in children as well as in adults. However, it is unclear whether this affects physical development according to the concentration of IGFBP-3.

Keyword

Body height; Insulin-like growth factor-binding protein 3; Polymorphism

MeSH Terms

Adult
Body Height
Child
Female*
Gene Frequency
Genotype
Growth Hormone
Humans
Insulin-Like Growth Factor Binding Protein 3
Insulin-Like Growth Factor I
Molar
Polymorphism, Single Nucleotide
Promoter Regions, Genetic
Reference Values
School Health Services
Seoul
Growth Hormone
Insulin-Like Growth Factor Binding Protein 3
Insulin-Like Growth Factor I

Figure

  • Fig. 1 A representative pattern of restriction fragment length polymorphism analysis on a gel indicates different genotypes in 4 individuals. A size marker (100-bp DNA ladder) is included in the far left lane.

  • Fig. 2 Mean insulin-like growth factor-binding protein-3 (IGFBP-3) levels in all participants according to the genotype at nucleotide -202 of IGFBP-3. In the AA genotype group, this concentration was significantly higher than in the AC and CC genotype groups (both P=0.002).

  • Fig. 3 The insulin-like growth factor-1 (IGF-I)/IGF-binding protein-3 (IGFBP-3) ratio in all participants according to the genotype at the -202 A/C IGFBP3 locus. The ratio was significantly lower in the AA genotype group than in the AC genotype group (P=0.033).

  • Fig. 4 Mean levels of insulin-like growth factor-1 (IGF-I), IGF-binding protein-3 (IGFBP-3), and IGF-I/IGFBP-3 ratio were compared according to group. IGF-I concentrations in groups 2 and 3 were significantly higher than in group 1 (P=0.011 and P=0.001). The IGFBP-3 concentration was significantly higher in group 3 than in group 1 (P=0.015). The IGF-I/IGFBP-3 ratio was significantly higher in groups 2 and 3 than in group 1 (P=0.029 and P=0.020). Group 1, 3rd percentile ≤ height <10th percentile; group 2, height = 50th percentile; group 3, 90th percentile ≤ height <97th percentile.


Cited by  2 articles

Effect of -202 A/C IGFBP-3 polymorphisms on growth responses in children with idiopathic short stature
Hye Ree Kang, Il Tae Hwang, Seung Yang
Ann Pediatr Endocrinol Metab. 2020;25(1):31-37.    doi: 10.6065/apem.2020.25.1.31.

Relationship between growth velocity and change of levels of insulin-like growth factor-1, insulin-like growth factor binding protein-3 and, IGFBP-3 promoter polymorphism during GnRH agonist treatment
Jun-Hong Park, Il-Tae Hwang, Seung Yang
Ann Pediatr Endocrinol Metab. 2020;25(4):234-239.    doi: 10.6065/apem.2040020.010.


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