title: The d3/fl-growth hormone (GH) receptor polymorphism does not influence the effect of GH treatment (66 microg/kg per day) or the spontaneous growth in short non-GH-deficient small-for-gestational-age children: results from a two-year controlled prospective study in 170 Spanish patients.
abstract: BACKGROUND
  The d3/fl-GH receptor (d3/fl-GHR, exon 3-deleted/full-length GHR) has recently been associated with responsiveness to GH therapy.
  
  
  OBJECTIVE
  The objective of the study was to evaluate whether the d3/fl-GHR genotypes influence the intensity of spontaneous and/or GH therapy-stimulated growth in small-for-gestational-age (SGA) patients.
  
  
  METHODS
  This was a 2-yr prospective, controlled, randomized trial.
  
  
  METHODS
  Thirty Spanish hospitals participated. Auxologic and GH secretion evaluation was hospital based, whereas molecular analyses and auxologic data computation were centralized.
  
  
  METHODS
  Patients included 170 short SGA children: 140 remained prepubertal and 30 entered puberty during the second follow-up year.
  
  
  METHODS
  Eighty-six were treated with GH (66 microg/kg.d) for 2 yr and 84 were not treated.
  
  
  METHODS
  Previous and 2-yr follow-up auxologic data were recorded at each hospital, d3/fl-GHR genotypes determined, and data analyzed for patients who remained prepubertal (group 1, 68 GH treated and 72 non-GH treated) and for all the patients (group 2).
  
  
  RESULTS
  In group 1 GH-treated patients, growth velocity, and height-sd score during the first and second years, total 2-yr height gain (18.5 +/- 2.4 cm in d3/d3; 18.4 +/- 2.6 in d3/fl; 19.5 +/- 2.3 in fl/fl), Delta 2-yr height increase (9.1 +/- 2.4 cm in d3/d3; 9.4 +/- 3.0 in d3/fl; 10.4 +/- 2.1 in fl/fl), first-year growth prediction and studentized residual values (0.08 +/- 1.26 in d3/d3; 0.28 +/- 1.21 in d3/fl; 0.67 +/- 0.95 in fl/fl) did not differ among the d3/fl-GHR genotypes. In group 1 non-GH-treated patients, neither growth velocity nor height-sd score changed significantly, and values were similar in each d3/fl-GHR genotype. Results in all patients (group 2) were similar to those in group 1.
  
  
  CONCLUSIONS
  In short non-GH-deficient SGA children, both spontaneous growth rate and responsiveness to 66 microg/k.d GH therapy were similar for each d3/fl-GHR genotype carried.
authors.affiliation: Servicio de Pediatría, Unidad de Endocrinología, Hospital Maternoinfantil Vall d'Hebron, Paseo Vall d'Hebron 119, 08035 Barcelona, Spain. ancarrascosa@vhebron.net
authors.forename: A
authors.initials: A
authors.lastname: Carrascosa
authors.forename: C
authors.initials: C
authors.lastname: Esteban
authors.forename: R
authors.initials: R
authors.lastname: Espadero
authors.forename: M
authors.initials: M
authors.lastname: Fernández-Cancio
authors.forename: P
authors.initials: P
authors.lastname: Andaluz
authors.forename: M
authors.initials: M
authors.lastname: Clemente
authors.forename: L
authors.initials: L
authors.lastname: Audí
authors.forename: H
authors.initials: H
authors.lastname: Wollmann
authors.forename: L
authors.initials: L
authors.lastname: Fryklund
authors.forename: L
authors.initials: L
authors.lastname: Parodi
mesh_terms: D001827:Body Height / Q000187:drug effects*; D002648:Child; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011986:Receptors, Somatotropin / Q000235:genetics*; D013030:Spain; D018709:Statistics, Nonparametric
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I