The exon3-deleted growth hormone receptor gene polymorphism (d3-GHR) is associated with insulin and spontaneous growth in short SGA children (NESGAS)

Wegmann, Mathilde Gersel; Thankamony, Ajay; Roche, Edna; Hoey, Hilary; Kirk, Jeremy; Shaikh, Guftar; Ivarsson, Sten; Söder, Olle; Juul, Anders; Jensen, Rikke Beck

doi:10.1016/j.ghir.2017.07.001

Cited by 9 publications

(5 citation statements)

References 43 publications

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“…Polymorphic variation in IGF binding protein-I and -3 axes may also play a role in the complex interaction between spontaneous growth, glucose homeostasis and lipid metabolism in short children born SGA [99,100]. Short SGA children carrying the d3-growth hormone receptor polymorphism had increased spontaneous growth, lower insulin sensitivity and a compensatory increase in glucose, C-peptide and insulin before GH therapy compared with children homozygous for the full-length allele [101].…”

Section: Heterogeneity Of Results Within and Between Studiesevidence mentioning

confidence: 99%

What is the evidence for beneficial effects of growth hormone treatment beyond height in short children born small for gestational age? A review of published literature

Darendelıler

Kandemir

Harris

et al. 2019

Journal of Pediatric Endocrinology and Metabolism

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BackgroundAn increasing body of evidence supports the view that both an adverse intrauterine milieu and rapid postnatal weight gain in children born small for gestational age (SGA) contribute towards the risk for the development of chronic diseases in adult life.ContentThe aim of this review was to identify and summarize the published evidence on metabolic and cardiovascular risk, as well as risk of impaired cardiac function, intellectual capacity, quality of life, pubertal development and bone strength among children born SGA. The review will then address whether growth hormone (GH) therapy, commonly prescribed to reduce the height deficit in children born SGA who do not catch up in height, increases or decreases these risks over time.SummaryOverall, there are limited data in support of a modest beneficial effect of GH therapy on the adverse metabolic and cardiovascular risk observed in short children born SGA. Evidence to support a positive effect of GH on bone strength and psychosocial outcomes is less convincing.OutlookFurther evaluation into the clinical relevance of any potential long-term benefits of GH therapy on metabolic and cardiovascular endpoints is warranted.

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Section: Heterogeneity Of Results Within and Between Studiesevidence mentioning

confidence: 99%

What is the evidence for beneficial effects of growth hormone treatment beyond height in short children born small for gestational age? A review of published literature

Darendelıler

Kandemir

Harris

et al. 2019

Journal of Pediatric Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…Table 2 summarizes the studies that have been published on the relationship between the GHR isoforms and SGA children. Numerous studies support the concept that the d3GHR isoform is linked to a significant increase in compensatory growth in SGA children [9,10] and a better growth response to hGH treatments [4,111]. However, other studies have also supported the lack of a connection between GHR genotypes and patients' responses to hGH therapy [12,112] (Table 2).…”

Section: Small For Gestational Age (Sga)mentioning

confidence: 96%

“…This isoform is characterized by increased receptor activity, enhanced signal transduction and altered hormone binding [5,6]. Several studies investigated how this polymorphism might affect growth [7][8][9][10]. Additionally, the clinical and biochemical phenotype of patients with GH abundance or deficiency, such as those with acromegaly, Turner syndrome, and small for gestational age (SGA), were studied, along with their responsiveness to particular treatments, and it was discovered that, depending on the syndrome under investigation, the presence or absence of the d3GHR polymorphism has a positive or negative impact, respectively, on GH concentrations following treatment [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

The Exon 3-Deleted Growth Hormone Receptor (d3GHR) Polymorphism - a Favorable Backdoor Mechanism for the GHR Function

Falah,

Sharvit,

Atzmon

2023

Preprint

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Growth hormone (GH) is a peptide hormone that plays a crucial role in controlling growth, development, and lifespan. Molecular regulation of GH is accomplished via the GH receptor (GHR) gene, which is the main factor influencing human development and is essential to optimal functioning of the GH/IGF-I axis. Two GHR isoforms have been studied, according to the presence (flGHR) or absence (d3GHR) of exon 3. The d3GHR variant, which has recently been related to longevity, is associated with enhanced signal transduction and higher receptor function. Many of these studies indicated that the growth response to GH treatment may be affected. Individuals carrying the d3GHR isoform have higher receptor activity, improved signal transduction, and alterations in the treatment response and efficacy compared with those carrying the WT isoform. Further, studies performed in patients with acromegaly, Prader-Willi syndrome, Turner syndrome, small for gestational age (SGA), and growth hormone deficiency (GHD) suggested that the d3GHR variant may have an impact on the relationship between GH and IGF-I levels, height, weight, BMI, and other variables. Other research, however, revealed inconsistent results, which might have been caused by confounding factors, including limited sample sizes and different experimental methods. In this review, we lay out the complexity of the GHR isoforms and provide an overview of the major pharmacogenetic research conducted on this ongoing and unresolved subject.

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“…Table 1 summarizes the studies that have been published on the relationship between the GHR isoforms and SGA children. Numerous studies support the concept that the d3GHR isoform is linked to a significant increase in compensatory growth in SGA children [ 7 , 8 ] and a better growth response to hGH treatments [ 2 , 92 ]. However, other studies have also supported the lack of a connection between GHR genotypes and patients’ responses to hGH therapy [ 10 , 93 ] ( Table 1 ).…”

Section: Effects Of the Flghr And D3ghr Isoforms On Various Growth Di...mentioning

confidence: 99%

“…This isoform is characterized by increased receptor activity, enhanced signal transduction and altered hormone binding [ 3 , 4 ]. Several studies investigated how this polymorphism might affect growth [ 5 , 6 , 7 , 8 ]. Additionally, the clinical and biochemical phenotype of patients with GH abundance or deficiency, such as those with GHD, PWS, acromegaly, Turner syndrome, and small for gestational age (SGA), were studied, along with their responsiveness to particular treatments.…”

Section: Introductionmentioning

confidence: 99%

The Exon 3-Deleted Growth Hormone Receptor (d3GHR) Polymorphism—A Favorable Backdoor Mechanism for the GHR Function

Falah,

Sharvit,

Atzmon

2023

IJMS

View full text Add to dashboard Cite

Growth hormone (GH) is a peptide hormone that plays a crucial role in controlling growth, development, and lifespan. Molecular regulation of GH is accomplished via the GH receptor (GHR), which is the main factor influencing human development and is essential to optimal functioning of the GH/IGF-I axis. Two GHR isoforms have been studied, according to the presence (flGHR) or absence (d3GHR) of exon 3. The d3GHR isoform, which lacks exon 3 has recently been related to longevity; individuals carrying this isoform have higher receptor activity, improved signal transduction, and alterations in the treatment response and efficacy compared with those carrying the wild type (WT) isoform (flGHR). Further, studies performed in patients with acromegaly, Prader–Willi syndrome, Turner syndrome, small for gestational age (SGA), and growth hormone deficiency (GHD) suggested that the d3GHR isoform may have an impact on the relationship between GH and IGF-I levels, height, weight, BMI, and other variables. Other research, however, revealed inconsistent results, which might have been caused by confounding factors, including limited sample sizes and different experimental methods. In this review, we lay out the complexity of the GHR isoforms and provide an overview of the major pharmacogenetic research conducted on this ongoing and unresolved subject.

show abstract

The exon3-deleted growth hormone receptor gene polymorphism (d3-GHR) is associated with insulin and spontaneous growth in short SGA children (NESGAS)

Cited by 9 publications

References 43 publications

What is the evidence for beneficial effects of growth hormone treatment beyond height in short children born small for gestational age? A review of published literature

What is the evidence for beneficial effects of growth hormone treatment beyond height in short children born small for gestational age? A review of published literature

The Exon 3-Deleted Growth Hormone Receptor (d3GHR) Polymorphism - a Favorable Backdoor Mechanism for the GHR Function

The Exon 3-Deleted Growth Hormone Receptor (d3GHR) Polymorphism—A Favorable Backdoor Mechanism for the GHR Function

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