title: Growth hormone (GH) dose, but not exon 3-deleted/full-length GH receptor polymorphism genotypes, influences growth response to two-year GH Therapy in Short Small-for-Gestational-Age Children.
abstract: BACKGROUND
  In short small-for-gestational-age (SGA) patients, the exon 3-deleted(d3)/full-length (fl)-GHR polymorphism was associated with responsiveness to GH therapy (30-48 microg/kg.d); however, these results were not confirmed for higher GH doses (56-66 microg/kg.d). We hypothesized that higher doses would mask the lower dose differences.
  
  
  OBJECTIVE
  Our objective was to evaluate, in short SGA patients, 2-yr growth response to GH therapy (32.1 +/- 3.8 microg/kg.d) according to exon d3/fl-GHR genotypes.
  
  
  METHODS
  This was a 2-yr follow-up study.
  
  
  METHODS
  There was a total of 60 short SGA children (d3/d3 n = 8, d3/fl n = 23, and fl/fl n = 29). There were 11 children that entered puberty during the second follow-up year. Results were evaluated for all patients (group A1, n = 60, 7.7 +/- 2.7 yr) and for patients who remained prepubertal (group A2, n = 49, 6.9 +/- 2.2 yr).
  
  
  METHODS
  Patients were followed by a single clinical team, and exon d3/fl-GHR genotypes were determined and analyzed in the same hospital.
  
  
  RESULTS
  In groups A1 and A2, growth velocity significantly (P < 0.0001) increased during the first and second years of therapy, as did height sd score (SDS). These increases were similar in each exon d3/fl-GHR genotype. Total 2-yr height gain (cm, SDS) did not differ statistically among genotypes: group A1, 15.0 +/- 2.0 cm and 1.15 +/- 0.45 SDS in d3/d3, 16.0 +/- 2.4 cm and 1.17 +/- 0.51 SDS in d3/fl, 16.1 +/- 2.4 cm and 1.15 +/- 0.53 SDS in fl/fl; and group A2, 15.4 +/- 2.0 cm and 1.03 +/- 0.42 SDS in d3/d3, 15.6 +/- 2.1 cm and 1.22 +/- 0.51 in d3/fl, and 16.2 +/- 2.6 cm and 1.21 +/- 0.56 SDS in fl/fl.
  
  
  CONCLUSIONS
  These results did not confirm our hypothesis and show that, in short SGA children, 2-yr growth response to GH therapy 32.1 +/- 3.8 microg/kg.d was similar for each exon d3/fl-GHR genotype carried, as occurred in our previous study using 66 microkg.d.
authors.affiliation: Department of Pediatrics, Institut de Recerca, Hospital Vall d'Hebron, Centre for Biomedical Research on Rare Diseases, Autonomous University, 08035, Barcelona, Spain. ancarrascosa@vhebron.net
authors.forename: Antonio
authors.initials: A
authors.lastname: Carrascosa
authors.forename: Laura
authors.initials: L
authors.lastname: Audí
authors.forename: Cristina
authors.initials: C
authors.lastname: Esteban
authors.forename: Mónica
authors.initials: M
authors.lastname: Fernández-Cancio
authors.forename: Pilar
authors.initials: P
authors.lastname: Andaluz
authors.forename: Miquel
authors.initials: M
authors.lastname: Gussinyé
authors.forename: María
authors.initials: M
authors.lastname: Clemente
authors.forename: Diego
authors.initials: D
authors.lastname: Yeste
authors.forename: María Angeles
authors.initials: MA
authors.lastname: Albisu
mesh_terms: D002648:Child; D005091:Exons; D005260:Female; D005838:Genotype; D006130:Growth Disorders / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D020249:Hormone Replacement Therapy / Q000379:methods*; D019382:Human Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D011110:Polymorphism, Genetic; D011986:Receptors, Somatotropin / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I