Analysis of cytosine adenine repeat polymorphism of the IGF-I promoter gene in children with idiopathic short stature / 소아과

PURPOSE: A polymorphism in the IGF-I gene promoter region is known to be associated with serum IGF-I levels, birth weight, and body length, suggesting that IGF-I gene polymorphism might influence postnatal growth. The present study aimed to investigate the role of this polymorphic cytosine-adenine (CA) repeat of the IGF-I gene in children with idiopathic short stature. METHODS: The study involved 131 children (72 boys and 59 girls) diagnosed with idiopathic short stature, aged 7-15 years. Genomic DNA was extracted from anticoagulated peripheral whole blood. The primers were designed to cover the promoter region containing the polymorphic CA repeat. Data were analyzed using GeneMapper software. The correlations between age and serum IGF-I levels were analyzed using Spearmans correlation coefficient. RESULTS: The CA repeat sequences ranged from 15 to 22 , with 19 CA repeats the most common with an allele frequency of 40.6%. Homozygous for 19 CA repeat was 13.0%, heterozygous for 19 CA repeat was 56.5%, and 19 CA non-carrier was 30.5%. The three different genotype groups showed no significant differences in height, body weight and body mass index, and serum IGF-I levels. The serum IGF-I level and age according to the IGF-I genotypes were significantly correlated in the entire group, 19 CA repeat carrier group, and the non-carrier group. The three groups also showed no significant differences in the first year responsiveness to GH treatment. CONCLUSION: There were no significant different correlations between 19 CA repeat polymorphism and serum IGF-I levels according to genotype. Our results suggest that the IGF-I 19 CA repeat gene polymorphism is not functional in children with idiopathic short stature.

Diagnostic Significance of Serum IGF-I Level in Growth Hormone Deficiency / 대한소아내분비학회지

PURPOSE:Insuline-like growth factor I(IGF-I) is polypeptide mitogen and mediate growth effect of growth hormone(GH). It's serum level is regulated by GH. The aim of this study is to evaluate whether -2 standard deviation of IGF-I level in normal short stature after insuline and L-dopa stimulation test has any diagnostic significance in GH deficiency. METHOD:We included 64 children with GH deficiency(complete GH deiciency 18 cases, partial GH deficiency 46 cases). Their height was below 10 percentile of korean children's standard growth chart. Control group was 175 children whose test results were normal after insuline and L-dopa stimulation test. Serum growth hormone level was measured by IRMA(immunoradiometric assay) with "Daiichi" kit(Japan) and serum IGF-I level was measured with 125I RIA kit (U.S.A). RESULTS: 1)Serum IGF-I level in normal stimulation test result group was increased with the age and the level was higher in female than that of male. 2)Using the cut-off value of -2SD of IGF-I level in control group, sensitivity was 17.2%, specificity was 98.86%, positive predictive value was 84.62%, negative predictive value was 76.55%, and test accuracy was 76.99%. Sensitivity and test accuracy was 44.44% and 93.26% in th complete GH deficiency, respectively. 3)Serum IGF-I level was significantly correlated with peak GH level with insuline stimulation test in control and GH deficiency group(Y=0.018889X+11.32 r= 0.23930 P=0.0014, Y=0.008592X+4.189 r=0.28141 P=0.0267). But serum IGF-I level was was not correlated with peak GH level with L-dopa stimulation test(Y= 0.005609X+13.88 r=0.06625 P=0.3823, Y=0.008293X+2.98 r=0.20895 P=0.1031). CONCLUSION: Serum IGF-I level in GH deficiency group was lower than that of control group and had wide variation of normal range. Based upon above results IGF-I level has limited clinical value in the diagnosis of GH deficiency.

Serum IGF-I, IGF-II and IGFBP-3 levels in children with isolated growth hormone deficiencies and panhypopituitarism.

Serum IGF-I,IGF-II and IGFBP-3 levels were measured by radio-immunometric assay in 24 children, 16 with isolated growth hormone deficiencies (GHD) and 8 with panhypopituitarism. AII serum parameters were significantly lower in panhypopituitarism than in isolated GHD. Serum IGF-I levels were lower than the normal range in 50 percent of the patients. However, 66.7 percent of isolated GHD children older than 10 years had serum IGF-I levels lower than the normal range. AII isolated GHD children had serum IGFBP-3 levels lower than the 50th percentile or mean of normal range. Combined IGF-I and IGF-II levels had no more advantage than IGF-L levels in the diagnosis of isolated GHD. Serum IGFII levels were lower than normal range in 87.5 percent. In conclusion, serum IGFBP-3 measurement is useful than IGF-I in all age groups. Low serum IGF-II levels and panhypopituitarism were demonstrated in this study.

The Concentration of Insulin Like Growth Factor-I(IGF-I) and IGF-Binding Protein-3 (IGFBP-3) in the Serum of Children with Growth Hormone Deficiency and the Alterations after Growth Hormone Treatment

PURPOSE: The insulin like growth factors (IGFs) circulate complexed to IGF-binding proteins(IGFBPs). IGFBP-3 is the major circulating IGFBP and is found primarily as a 150 kDa complex which contains an acid labile subunit(ALS), IGFBP-3, and IGF-I or IGF-II and is considered to be growth hormone(GH) dependent. In this study, we measured serum IGF-I, IGFBP-3 and 150 kDa levels in sera of growth hormone deficient children(GHD) before and after GH treatment respectively to clarify the utility of these factors as a diagnostic marker for GHD and to observe the alterations of these factors according to GH treatment. METHODS: Measurement of serum IGF-I, IGFBP-3 and 150 kDa complex were performed in 10 children with complete growth hormonr deficiency(cGHD), in 6 children with partial growth hormone deficiency(pGHD) and in 10 normal healthy subjects. Serum IGF-I was measured by radioimmunoassay (RIA). IGF-I was seperated from IGFBPs by Sephadex G-50 acid chromatography. Serum IGFBP-3 was assessed by Western ligand blot(WLB) analysis as described by Hossenlopp with minor modifications. To evaluate alterations of different molecular size classes of IGF-BP complexes according to GH treatment, WLB was done after neutral size-exclusion chromatography using Sephacryl S-200. RESULTS: 1) The serum IGF-I level in children with GHD was significantly lower than that of control subjects(96.2+/-40.1 ng/ml vs 147.5+/-37.9 ng/ml)(p0.05). 3) The serum IGFBP-3 level is markedly decreased in 9 of 10 children with cGHD, but only in 2 of 6 children with pGHD which was measured by WLB method. 4) The serum IGF-I level after GH treatment was increased significantly in children with GHD(138.7+/-49.2 ng/ml vs 78.7+/-23.4 ng/ml)(p<0.01). The serum IGFBP-3 level was also increased after GH treatment as similar pattern. 5) The marked decrement of serum IGFBP-3 level in children with cGHD was explained as the result of decline in the 150 kDa IGFBP complex, and after GH treatment 150 kDa complex was increased; in the 150 kDa IGFBP complex, free IGF-I binding sites were increased. CONCLUSIONS: The serum levels of IGF-I, IGFBP-3 and 150 kDa complex in children with cGHD were decreased significantly, but in children with pGHD these changes were not observed as prominant as cGHD. These findings suggest that the measurments of serum IGF-I, IGFBP-3 level may be useful not only in the diagnosis of GHD but also differentiate cGHD from pGHD and the serum IGFBP-3 level may be more sensitive for diagnosing GHD even though each test by itself has a limited diagnostic accuracy as a single test.