title: The interactive effect of GHR-exon 3 and -202 A/C IGFBP3 polymorphisms on rhGH responsiveness and treatment outcomes in patients with Turner syndrome.
abstract: BACKGROUND
  There is great interindividual variability in the response to recombinant human (rh) GH therapy in patients with Turner syndrome (TS). Ascertaining genetic factors can improve the accuracy of growth response predictions.
  
  
  OBJECTIVE
  The objective of the study was to assess the individual and combined influence of GHR-exon 3 and -202 A/C IGFBP3 polymorphisms on the short- and long-term outcomes of rhGH therapy in patients with TS.
  
  
  METHODS
  GHR-exon 3 and -202 A/C IGFBP3 genotyping (rs2854744) was correlated with height data of 112 patients with TS who remained prepubertal during the first year of rhGH therapy and 65 patients who reached adult height after 5 ± 2.5 yr of rhGH treatment.
  
  
  METHODS
  First-year growth velocity and adult height were measured.
  
  
  RESULTS
  Patients carrying at least one GHR-d3 or -202 A-IGFBP3 allele presented higher mean first-year growth velocity and achieved taller adult heights than those homozygous for GHR-fl or -202 C-IGFBP3 alleles, respectively. The combined analysis of GHR-exon 3 and -202 A/C IGFBP3 genotypes showed a clear nonadditive epistatic influence on adult height of patients with TS treated with rhGH (GHR-exon 3 alone, R² = 0.27; -202 A/C IGFBP3, R² = 0.24; the combined genotypes, R² = 0.37 at multiple linear regression). Together with clinical factors, these genotypes accounted for 61% of the variability in adult height of patients with TS after rhGH therapy.
  
  
  CONCLUSIONS
  Homozygosity for the GHR-exon3 full-length allele and/or the -202C-IGFBP3 allele are associated with less favorable short- and long-term growth outcomes after rhGH treatment in patients with TS.
authors.affiliation: Faculdade de Medicina da Universidade de Sao Paulo, (LIM-25), Avenida Dr. Arnaldo, 455 5 degree andar sala 5340, CEP 01246-903 São Paulo-SP, Brazil. alexj@usp.br
authors.forename: Adriana F
authors.initials: AF
authors.lastname: Braz
authors.forename: Everlayny F
authors.initials: EF
authors.lastname: Costalonga
authors.forename: Luciana R
authors.initials: LR
authors.lastname: Montenegro
authors.forename: Ericka B
authors.initials: EB
authors.lastname: Trarbach
authors.forename: Sonir R R
authors.initials: SR
authors.lastname: Antonini
authors.forename: Alexsandra C
authors.initials: AC
authors.lastname: Malaquias
authors.forename: Ester S
authors.initials: ES
authors.lastname: Ramos
authors.forename: Berenice B
authors.initials: BB
authors.lastname: Mendonca
authors.forename: Ivo J P
authors.initials: IJ
authors.lastname: Arnhold
authors.forename: Alexander A L
authors.initials: AA
authors.lastname: Jorge
mesh_terms: D000328:Adult; D000483:Alleles; D001827:Body Height / Q000187:drug effects; D001938:Brazil; D004351:Drug Resistance; D005091:Exons; D005260:Female; D017353:Gene Deletion; D056726:Genetic Association Studies; D006720:Homozygote; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000235:genetics / Q000627:therapeutic use*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011986:Receptors, Somatotropin / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome; D014424:Turner Syndrome / Q000188:drug therapy* / Q000235:genetics*
chemical_list: C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D019382:Human Growth Hormone