CoChat
Sign Up
Cited by 165Growth Hormone and Insulin-like Growth FactorsHypothalamic control of reproductive hormonesPituitary Gland Disorders and Treatments

The d3-growth hormone (GH) receptor polymorphism is associated with increased responsiveness to GH in Turner syndrome and short small-for-gestational-age children

Binder, G., Baur, F., Schweizer, R., Ranke, M. B.·2006·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2005-1581
Open this paper in CoChat — free account

Abstract

CONTEXT: A protein polymorphism of the GH receptor (GHR) based on the genomic deletion of exon 3 (d3-GHR) has recently been linked to the magnitude of growth response to high-dose recombinant human GH (rhGH) therapy of short children without GH deficiency. OBJECTIVE: This study tests the novel association in two distinct groups of rhGH-treated patients, short girls with Turner syndrome and short children born small for gestational age (SGA). DESIGN: The retrospective study included all children who were treated with rhGH during the last 18 yr at our hospital. PATIENTS: Patients with Turner syndrome were defined by the specific karyotype (n = 53), short children born SGA were determined by birth length and/or weight less than -2.0 sd score and a height at start of rhGH therapy less than -2.0 sd score (n = 60). Exclusion criteria were puberty, an age less than 3.5 or more than 14 yr, and GH deficiency. MATERIALS AND METHODS: Growth prediction for the first year of therapy was calculated on the basis of rhGH dose, age, weight, height, and gender-adjusted midparental height according to the prediction models by Ranke et al. The GHR-exon 3 locus was genotyped using a PCR multiplex assay. GH, IGF-I, and IGF binding protein 3 (IGFBP-3) were measured by RIA. INTERVENTION: For growth promotion, a mean rhGH dose of 38 mug/kg.d (sd, +/-8) was administered in Turner syndrome patients and 56 mug/kg.d (sd, +/-11) in short children born SGA. RESULTS: No significant difference in height, spontaneous height velocity, IGF-I, and IGFBP-3 levels was found at the start of rhGH therapy in the three GHR genotype groups studied. At the first year of treatment, girls with Turner syndrome carrying one or two d3-GHR alleles showed a significantly higher increment in height velocity (P = 0.019) and exceeded their growth prediction significantly (P = 0.007), whereas their increments of IGF-I and IGFBP-3, weight, and height were not significantly different. Carriers of d3-GHR in the group of short children born SGA grew significantly faster than predicted (P = 0.023). However, in comparison to the carriers of full-length GHR, gain of height velocity was not significantly higher (P = 0.067). The mean gain of height associated with d3-GHR accounted for approximately 0.75 cm in SGA and 1.5 cm in Turner syndrome during the first year of rhGH therapy. CONCLUSIONS: Our data support the theory that there is increased responsiveness to high-dose rhGH in association with the d3-GHR genotype. The magnitude of this effect may depend on the primary origin of the short stature.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1210/jc.2005-1581

Cites

30 of 30 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Results from studies of girls with TS are contradictory regarding the effect of d3 alleles on growth response.

    “However, the results from studies of girls with TS are contradictory with some finding a significant effect on height velocity, total gain in height and adult height in girls with TS carrying one or two d3 alleles.130-132 Other studies did not find an effect.133-135”

    From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [130]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Binder, G., Baur, F., Schweizer, R., & Ranke, M. B.
Affiliations
University Children's Hospital Tübingen (DE)
Corresponding author
Binder, G.
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2006-02
Volume
91
Issue
2
Pages
659-664
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2005-1581
OpenAlex
W1988159556
Cited by
165
References
30
Citations by year
2026: 2 · 2025: 1 · 2024: 2 · 2023: 6 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 3 · 2015: 8 · 2014: 5 · 2013: 9 · 2012: 8
FWCI
16.08
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
Pfizer
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
Keywords
Turner syndrome, small for gestational age, recombinant human growth hormone therapy, growth response, height velocity, insulin-like growth factor I, IGFBP-3, growth prediction, short stature, genotype-phenotype correlation, IGF-I/IGFBP-3 ratio
MeSH terms
Child, DNA, Exons, Female, Genotype, Humans, Insulin-Like Growth Factor I, Male, Polymorphism, Genetic, Receptors, Somatotropin, Retrospective Studies, Turner Syndrome, Polymerase Chain Reaction, Insulin-Like Growth Factor Binding Protein 3, Human Growth Hormone

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review