title: Influence of the d3-growth hormone (GH) receptor isoform on short-term and long-term treatment response to GH replacement in GH-deficient adults.
abstract: OBJECTIVE
  Recombinant human GH (rhGH) replacement in adults is aimed at improving signs and symptoms of the adult GH deficiency (GHD) syndrome. In children, a common polymorphism of the GH receptor (exon-3 deletion, d3GHR) increases the response to rhGH replacement. The aim of this study was to assess the effects of this polymorphism on the response to rhGH replacement in adults.
  
  
  METHODS
  Prospective intervention with rhGH during 1 yr (n = 99) and in a subset during 5 yr (n = 53).
  
  
  METHODS
  The presence of the d3GHR variant was established in GHD patients and linked to short-term and long-term effects of rhGH replacement on IGF-I, lipid metabolism, anthropometric parameters, and bone mineral density.
  
  
  RESULTS
  Fifty-five patients had two wild-type alleles (56%), whereas 38 patients (38%) had one allele and six patients (6%) had two alleles coding the d3GHR isoform. During short-term rhGH replacement, the increase in IGF-I was higher in patients bearing at least one d3GHR allele, compared with those with two wild-type alleles (at an identical mean dose of rhGH). The decrease in total cholesterol and low-density lipoprotein cholesterol was lower in the group bearing at least one d3GHR allele, whereas the increase in high-density lipoprotein cholesterol was higher, compared with patients with the wild-type genotype. In contrast, these differential responses of GHR genotype could not be demonstrated during long-term rhGH replacement.
  
  
  CONCLUSIONS
  The d3GHR genotype contributes, at least for some parameters, to the interindividual differences in efficacy of short-term, but not long-term, rhGH replacement in adults with GHD.
authors.affiliation: Department of Endocrinology and Metabolic Diseases C4-R, Leiden University Medical Center, Leiden, The Netherlands. a.a.van_der_klaauw@lumc.nl
authors.forename: Agatha A
authors.initials: AA
authors.lastname: van der Klaauw
authors.forename: Tahar
authors.initials: T
authors.lastname: van der Straaten
authors.forename: Renee
authors.initials: R
authors.lastname: Baak-Pablo
authors.forename: Nienke R
authors.initials: NR
authors.lastname: Biermasz
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Guchelaar
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Pereira
authors.forename: Johannes W A
authors.initials: JW
authors.lastname: Smit
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D015519:Bone Density; D005260:Female; D005838:Genotype; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011446:Prospective Studies; D020033:Protein Isoforms; D011986:Receptors, Somatotropin / Q000235:genetics*
chemical_list: D020033:Protein Isoforms; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone