Association of the (CA)<sub>n</sub> repeat polymorphism of insulin‐like growth factor‐I and −202 A/C IGF‐binding protein‐3 promoter polymorphism with adult height in patients with severe growth hormone deficiency

Miletta, Maria Consolata; Scheidegger, Ursina; Giordano, Mara; Bozzola, Mauro; Pagani, Sara; Bona, Gianni; Dattani, Mehul; Hindmarsh, Peter C.; Petkovic, Vibor; Oser-Meier, Monika; Flück, Christa E.; Mullis, Primus Ε.

doi:10.1111/j.1365-2265.2011.04267.x

Cited by 11 publications

(6 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Deregulation of IGF-1 expression may lead to a wide variety of human disorders (1). Many studies have also reported the association between P1 promoter polymorphisms, IGF-1 blood level and such diseases as diabetes, cancers and cardiova-scular diseases (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). In the present study, we examined the association between IGF-1 P1 promoter polymorphisms, IGF-1 levels and growth disorders in children.…”

Section: Discussionmentioning

confidence: 88%

“…The most common allele (in Caucasian populations) contains 19 repeats (12). Polymorphism of promoter CA di-nucleotide repeats has been associated with IGF-1 serum level, birthweight and body height and with such diseases as diabetes, cancer and cardiovascular diseases (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). On the other hand, the relation between the CA repeat polymorphism and IGF-1 level depends on race and ethnicity (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Polymorphisms in the P1 promoter of the IGF-1 gene in children with growth disorders

Broniarczyk

Kędzia

Nowak³

et al. 2014

Pediatr Endocrino Diabetes Metab

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Polymorphisms in the P1 promoter of the IGF-1 gene in children with growth disorders

Broniarczyk

Kędzia

Nowak³

et al. 2014

Pediatr Endocrino Diabetes Metab

View full text Add to dashboard Cite

show abstract

“…When looking at other components of the GH/IGF axis in prepubertal children with severe GHD, the Ϫ202 A/C polymorphism in the IGFBP3 promoter has also been associated with an increased IGFBP3 concentration and a greater height velocity in the first year of treatment in patients homozygous for the AA (13.0 Ϯ 2.1 cm/yr) compared with those with the AC (11.4 Ϯ 2.5 cm/yr) or CC (10.8 Ϯ 1.9 cm/yr) genotypes (307). Despite this early effect, the Ϫ202A/C IGFBP3 polymorphism does not seem to have an impact on adult height (307,308). More recently, Costalonga et al (309) reported that in patients with GHD, either isolated or combined with other pituitary hormone deficiencies, almost 4% of the variability in growth velocity during the first year of treatment can be explained by the variable length of polymorphic cytosineadenosine repeats (CA) 10 In the era of genome-wide associations and next-generation sequencing, there is still a distinct lack of studies with enough statistical power to demonstrate which, if any, combination of genotypes may explain the variability in the response to rhGH treatment and affect its impact on adult height in patients with GHD of various etiologies.…”

Section: B Pharmacogenomics In Children With Ghdmentioning

confidence: 99%

Isolated Growth Hormone Deficiency (GHD) in Childhood and Adolescence: Recent Advances

et al. 2014

View full text Add to dashboard Cite

The diagnosis of GH deficiency (GHD) in childhood is a multistep process involving clinical history, examination with detailed auxology, biochemical testing, and pituitary imaging, with an increasing contribution from genetics in patients with congenital GHD. Our increasing understanding of the factors involved in the development of somatotropes and the dynamic function of the somatotrope network may explain, at least in part, the development and progression of childhood GHD in different age groups. With respect to the genetic etiology of isolated GHD (IGHD), mutations in known genes such as those encoding GH (GH1), GHRH receptor (GHRHR), or transcription factors involved in pituitary development, are identified in a relatively small percentage of patients suggesting the involvement of other, yet unidentified, factors. Genome-wide association studies point toward an increasing number of genes involved in the control of growth, but their role in the etiology of IGHD remains unknown. Despite the many years of research in the area of GHD, there are still controversies on the etiology, diagnosis, and management of IGHD in children. Recent data suggest that childhood IGHD may have a wider impact on the health and neurodevelopment of children, but it is yet unknown to what extent treatment with recombinant human GH can reverse this effect. Finally, the safety of recombinant human GH is currently the subject of much debate and research, and it is clear that long-term controlled studies are needed to clarify the consequences of childhood IGHD and the long-term safety of its treatment.

show abstract

“…It has been reported that IGFBP3 -202A/C variances can affect promoter activity and IGFBP3 levels. Several studies performed in healthy controls, adult GH-deficient patients, and in patients with cancer (22–25) showed a higher promoter activity (and higher IGFBP3 circulating levels) in AA>AC>CC genotypes. Our study had similar results.…”

Section: Discussionmentioning

confidence: 99%

Influence of the IGFBP3-202A/C Gene Polymorphism on Clinical Features and Surgery Outcome in Acromegalic Patients

Gao¹,

Zhu²,

Li³

et al. 2018

Front. Endocrinol.

View full text Add to dashboard Cite

Purpose: Excess growth hormone (GH) secretion in acromegaly patients results in increased levels of IGF-1 expression, which causes the clinical manifestations of acromegaly. IGF-1 levels are attenuated by IGFBP3, and a polymorphism in the promoter of IGFBP3 is known to affect the circulating level of IGFBP3 protein. The aim of the study was to evaluate the association of the IGFBP3 gene polymorphism with clinical features and surgery outcomes in acromegaly. We also investigate the difference in IGFBP3 polymorphism between acromegaly and general population.Methods: The study included 102 acromegalic patients and 142 sex- and age-matched healthy controls. The genotyping of IGFBP3 was carried out using the MassARRAY method. Patients were followed up for 4–12 months to estimate the neurosurgical effects. Clinical data were obtained from the medical records.Results: The CC genotype, which is associated with decreased IGFBP3 levels, was less common in acromegaly patients than among the healthy controls; although, this correlation was not significant (P = 0.056). There was no association of the IGFBP3 gene polymorphism with glucose, lipid, phosphorus, blood urea nitrogen, creatinine or uric acid levels. Additionally, there was no association between tumor size, texture, or hemorrhage/cyst, except there was a trend that more patients with the C allele (P = 0.054) needed additional treatment post-operation than did patients carrying the A allele (OR 1.985, 95% CI 0.983–4.008). Moreover, higher IGF-1 values after treatment were observed in patients carrying the C allele (P = 0.012 and P = 0.014 according to the additive model and dominant model, respectively).Conclusion: Polymorphisms in IGFBP3 may not influence metabolic parameters or pituitary tumor characteristics in acromegalic patients, but they may be associated with the hormone levels and surgery effects.

show abstract

Association of the (CA)_n repeat polymorphism of insulin‐like growth factor‐I and −202 A/C IGF‐binding protein‐3 promoter polymorphism with adult height in patients with severe growth hormone deficiency

Abstract: Our results indicate that in patients with severe IGHD, although the various IGF-I and IGFBP-3 genotypes may play a role in GH responsiveness, there was no effect on final height.

Cited by 11 publications

References 40 publications

Polymorphisms in the P1 promoter of the IGF-1 gene in children with growth disorders

Polymorphisms in the P1 promoter of the IGF-1 gene in children with growth disorders

Isolated Growth Hormone Deficiency (GHD) in Childhood and Adolescence: Recent Advances

Influence of the IGFBP3-202A/C Gene Polymorphism on Clinical Features and Surgery Outcome in Acromegalic Patients

Contact Info

Product

Resources

About

Association of the (CA)n repeat polymorphism of insulin‐like growth factor‐I and −202 A/C IGF‐binding protein‐3 promoter polymorphism with adult height in patients with severe growth hormone deficiency

Abstract: Our results indicate that in patients with severe IGHD, although the various IGF-I and IGFBP-3 genotypes may play a role in GH responsiveness, there was no effect on final height.

Cited by 11 publications

References 40 publications

Polymorphisms in the P1 promoter of the IGF-1 gene in children with growth disorders

Polymorphisms in the P1 promoter of the IGF-1 gene in children with growth disorders

Isolated Growth Hormone Deficiency (GHD) in Childhood and Adolescence: Recent Advances

Influence of the IGFBP3-202A/C Gene Polymorphism on Clinical Features and Surgery Outcome in Acromegalic Patients

Contact Info

Product

Resources

About

Association of the (CA)_n repeat polymorphism of insulin‐like growth factor‐I and −202 A/C IGF‐binding protein‐3 promoter polymorphism with adult height in patients with severe growth hormone deficiency