PMID- 16291706
OWN - NLM
STAT- MEDLINE
DCOM- 20060314
LR  - 20061115
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 91
IP  - 2
DP  - 2006 Feb
TI  - The d3-growth hormone (GH) receptor polymorphism is associated with increased 
      responsiveness to GH in Turner syndrome and short small-for-gestational-age 
      children.
PG  - 659-64
AB  - 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.
FAU - Binder, G
AU  - Binder G
AD  - Pediatric Endocrinology Section, University-Children's Hospital, 
      Hoppe-Seyler-Strasse 1, 72076 Tubingen, Germany. 
      gerhard.binder@med.uni-tuebingen.de
FAU - Baur, F
AU  - Baur F
FAU - Schweizer, R
AU  - Schweizer R
FAU - Ranke, M B
AU  - Ranke MB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051115
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Insulin-Like Growth Factor Binding Protein 3)
RN  - 0 (Receptors, Somatotropin)
RN  - 12629-01-5 (Human Growth Hormone)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Child
MH  - DNA/chemistry/genetics
MH  - Exons/genetics
MH  - Female
MH  - Genotype
MH  - Human Growth Hormone/blood/*therapeutic use
MH  - Humans
MH  - Insulin-Like Growth Factor Binding Protein 3/blood
MH  - Insulin-Like Growth Factor I/metabolism
MH  - Male
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Genetic
MH  - Receptors, Somatotropin/*genetics
MH  - Retrospective Studies
MH  - Turner Syndrome/blood/*drug therapy/*genetics
EDAT- 2005/11/18 09:00
MHDA- 2006/03/15 09:00
CRDT- 2005/11/18 09:00
PHST- 2005/11/18 09:00 [pubmed]
PHST- 2006/03/15 09:00 [medline]
PHST- 2005/11/18 09:00 [entrez]
AID - jc.2005-1581 [pii]
AID - 10.1210/jc.2005-1581 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2006 Feb;91(2):659-64. doi: 10.1210/jc.2005-1581. Epub 
      2005 Nov 15.