Genetic and epigenetic variability in the gene for IGFBP-3 (IGFBP3): Correlation with serum IGFBP-3 levels and growth in short children born small for gestational age

Kaay, Daniëlle C M van der; Hendriks, Emile; Ester, Wietske A.; Leunissen, Ralph W. J.; Willemsen, Ruben H.; Kort, Sandra W K de; Paquette, Jean; Hokken-Koelega, Anita C S; Deal, Cheri

doi:10.1016/j.ghir.2008.08.010

Cited by 35 publications

(16 citation statements)

References 48 publications

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“…In a preliminary study, the A allele did not increase the serum concentration of IGFBP-3, compared to the C allele12). However, in this study, a higher serum concentration of IGFBP-3 was observed in medium and short stature individuals with the AA genotype compared to those with the AC genotype, as seen in previous reports5619).…”

Section: Discussionsupporting

confidence: 87%

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

Park

Hwang

et al. 2017

Ann Pediatr Endocrinol Metab

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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.

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Section: Discussionsupporting

confidence: 87%

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

Park

Hwang

et al. 2017

Ann Pediatr Endocrinol Metab

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“…For the –202 IGFBP3 A/C polymorphism in the IGFBP3 gene, a clear trend of decreasing IGFBP-3 concentration per copy of the C allele has consistently been reported in adult [5,6,7,8,9,10] and pediatric [11,12] populations. Cord plasma levels of hormones and hormone-like substances, such as the IGFs and IGFBPs, reflect their intrauterine synthesis.…”

Section: Discussionmentioning

confidence: 94%

“…In several studies, the –202 A/C polymorphism was consistently shown to be associated with circulating levels of IGFBP-3. Until now, these associations have only been reported in adult [5,6,7,8,9,10] and pediatric populations [11,12]. …”

Section: Introductionmentioning

confidence: 99%

Influence of Polymorphisms in Genes Encoding for Insulin-Like Growth Factor (IGF)-I, Insulin, and IGF-Binding Protein (IGFBP)-3 on IGF-I, IGF-II, and IGFBP-3 Levels in Umbilical Cord Plasma

Landmann¹,

Kollerits

Kreuder

et al. 2012

Horm Res Paediatr

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Background/Aims: In postnatal life, polymorphisms in the promoter region of IGFBP3 were associated with insulin-like growth factor binding protein (IGFBP)-3 plasma levels. Whether these associations exist in utero has not been studied yet. Polymorphisms in the IGF1 promoter (polymorphic CA-repeat) and the insulin gene variable number tandem repeats locus (INS VNTR) are further polymorphisms of interest, because associations with birth weight have been reported. We aimed to investigate associations between polymorphisms in the promoter regions of IGF1 (wild type 192 bp), IGFBP3 (rs2854744; rs13241830), and INS VNTR (rs689) with cord plasma levels of IGF-I, IGF-II, and IGFBP-3. Methods: We measured IGF-I, IGF-II, and IGFBP-3 concentrations in cord blood from 677 neonates and genotyped the selected polymorphisms. Results: Carriers of the minor allele of both polymorphisms in the IGFBP3 gene had, on average, 4–5% lower IGFBP-3 levels per copy of the respective minor allele (p = 0.002 and p = 0.028) when compared to wild type carriers. The IGF1 promoter and the INS VNTR polymorphisms were not associated with IGF-I, IGF-II, or IGFBP-3 levels. Conclusions: Our data show associations of cord plasma IGFBP-3 levels and the IGFBP3 gene variants but not of IGF1 promoter and INS VNTR polymorphisms with IGF-I, IGF-II, or IGFBP-3 levels in utero.

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Section: Predicting the Growth Response With Genetic And Proteomic/mementioning

confidence: 99%

“…Twin studies showed that 60% of the interindividual variability in circulating IGFBP-3 levels is attributable to uncharacterized genetic factors [56], and in fact associations were found with two polymorphisms in IGFBP3 [57,58]. The 1st-year change in height SDS in short SGA children was associated with IGFBP-3 SDS, TH SDS, IGF-I SDS, age, and C-202/C-185 haplotype, explaining 52% of total variation in the 1st-year growth response [58]. With respect to circulating IGF-I, the proportion of variance attributable to genetic effects has been estimated at 38% [56], and there was a haplotype effect of the IGF1 promoter on serum IGF-I concentration [59].…”

Section: Predicting the Growth Response With Genetic And Proteomic/mementioning

confidence: 99%

Personalized Approach to Growth Hormone Treatment: Clinical Use of Growth Prediction Models

Wit¹,

Ranke²,

Albertsson‐Wikland³

et al. 2013

Horm Res Paediatr

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The goal of growth hormone (GH) treatment in a short child is to attain a fast catch-up growth toward the target height (TH) standard deviation score (SDS), followed by a maintenance phase, a proper pubertal height gain, and an adult height close to TH. The short-term response variable of GH treatment, first-year height velocity (HV) (cm/year or change in height SDS), can either be compared with GH response charts for diagnosis, age and gender, or with predicted HV based on prediction models. Three types of prediction models have been described: the Kabi International Growth Hormone Study models, the Gothenburg models and the Cologne model. With these models, 50-80% of the variance could be explained. When used prospectively, individualized dosing reduces the variation in growth response in comparison with a fixed dose per body weight. Insulin-like growth factor-I-based dose titration also led to a decrease in the variation. It is uncertain whether adding biochemical, genetic or proteomic markers may improve the accuracy of the prediction. Prediction models may lead to a more evidence-based approach to determine the GH dose regimen and may reduce the drug costs for GH treatment. There is a need for user-friendly software programs to make prediction models easily available in the clinic.

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Genetic and epigenetic variability in the gene for IGFBP-3 (IGFBP3): Correlation with serum IGFBP-3 levels and growth in short children born small for gestational age

Cited by 35 publications

References 48 publications

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

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

Influence of Polymorphisms in Genes Encoding for Insulin-Like Growth Factor (IGF)-I, Insulin, and IGF-Binding Protein (IGFBP)-3 on IGF-I, IGF-II, and IGFBP-3 Levels in Umbilical Cord Plasma

Personalized Approach to Growth Hormone Treatment: Clinical Use of Growth Prediction Models

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