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

Abstract

PurposeThe 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.MethodsRestriction 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.ResultsThe 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).ConclusionIn 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.

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

“…These results echo those from a previous study performed in Korean children. 19) Other prior studies described frequencies of the -202 A/C IGFBP-3 genotype in a European population as 16%-23% AA, 53%-64% AC, and 20%-24% CC, 20,21) with frequencies of 56%-63% AA, 32%-39% AC, and 5% CC reported in East Asians, 22,23) similar to this study. These results imply genotypic variation according to ethnicity or race, with the C allele being relatively prevalent in Europeans (Table 3).…”

“…In a previous study, serum IGFBP-3 levels differed significantly depending on genotype; however, the IGF-1/IGFBP-3 ratio was not different. 14,19) These findings suggest that serum IGF-1 concentrations reflect neither systemically nor locally produced IGF-1, and that variation at the -202 IGFBP-3 locus does not directly affect serum IGF-1 or free IGF-1 levels.…”

“…18) Genotyping of the IGFBP-3 locus was accomplished by restriction fragment length polymorphism analysis, as previously described. 19) Identification of the -202 A/ C IGFBP-3 allele was based on expected sizes of 242 bp and 162 bp for AA; 288 bp and 162 bp for CC; and 288, 242, and 162 bp for AC.…”

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

“…3 promoter polymorphism on physical development in the Korean girls; however, its effect was unclear (12).…”

“…Another study revealed the effect of -202 A/C IGFBP-3 promoter polymorphism on the physical development of Korean females. However, its effect was unclear [ 12 ].…”