title: Common polymorphisms of the growth hormone (GH) receptor do not correlate with the growth response to exogenous recombinant human GH in GH-deficient children.
abstract: BACKGROUND
  GH acts through the GH receptor (GHR), whose polymorphisms might affect the growth response to recombinant human GH (rhGH).
  
  
  OBJECTIVE
  The objective of this study was to investigate possible influences of GHR polymorphisms on the growth response to rhGH in GH-deficient (GHD) children.
  
  
  METHODS
  This was a 2-yr study (first year, spontaneous growth; second year, growth during rhGH treatment).
  
  
  METHODS
  This study was performed at a referral center.
  
  
  METHODS
  Fifty-four prepubertal GHD children (11 females; mean age, 7.8 yr; sd, 3.96) were studied.
  
  
  METHODS
  Patients were treated with rhGH (0.2 mg/kg.wk) for at least 1 yr after diagnosis. Growth velocity (GV) was measured 1 yr before treatment and during the first treatment year. GHR exons were amplified by PCR using pairs of intronic primers. The presence of single or multiple mismatches in the PCR products was revealed by denaturing high-pressure liquid chromatography. For exons in which mismatches were found by denaturing high-pressure liquid chromatography, direct sequencing was performed by automatic sequencer.
  
  
  METHODS
  Before the start of treatment, the mean height (Ht) sd score was -1.93 (sd, 0.70), and the mean GV sd score was -1.49 (sd, 1.26).
  
  
  RESULTS
  The posttreatment (first 12 months) mean GV sd score was 3.55 (sd, 3.27). Molecular analysis revealed a high frequency of GHR polymorphisms; in particular: exon 3 deletion (Del 3) in 26 subjects (48%), polymorphism 504 A>G at codon 168 of exon 6 in 44 (82%), and polymorphism 1576 A>C at codon 526 of exon 10 in 35 (65%). In most patients, these different polymorphisms recurred in association. We found no significant differences in GV between the groups of subjects defined by the polymorphic genotypes.
  
  
  CONCLUSIONS
  The most common GHR polymorphisms, alone or in association, do not appear to affect the growth response to rhGH in GHD children.
authors.affiliation: Department of Pediatrics, University of Brescia, 25123 Brescia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Pilotta
authors.forename: P
authors.initials: P
authors.lastname: Mella
authors.forename: M
authors.initials: M
authors.lastname: Filisetti
authors.forename: B
authors.initials: B
authors.lastname: Felappi
authors.forename: E
authors.initials: E
authors.lastname: Prandi
authors.forename: G
authors.initials: G
authors.lastname: Parrinello
authors.forename: L D
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: F
authors.initials: F
authors.lastname: Buzi
mesh_terms: D002648:Child; D005260:Female; D006128:Growth / Q000235:genetics; D006130:Growth Disorders / Q000188:drug therapy*; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011986:Receptors, Somatotropin / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D019382:Human Growth Hormone