title: SNPs within the GH-signaling pathway are associated with the early IGF1 response to GH replacement therapy in GHD adults.
abstract: OBJECTIVE
  GH-deficient (GHD) adults have reduced serum concentrations of IGF1. GH replacement therapy increases serum IGF1 concentrations, but the interindividual variation in treatment response is large and likely influenced by genetic factors. This study was designed to test the hypothesis that single-nucleotide polymorphisms (SNPs) in genes within the GH signaling pathway influence the serum IGF1 response to GH replacement.
  
  
  METHODS
  A total of 313 consecutive GHD adults (58.1% men; mean age 49.7 years) were studied before and after 1 week, 6 months, and 1 year of GH treatment. GH dose was individually titrated to normalize serum IGF1 levels. Six SNPs in the GH receptor (GHR) and the GH signaling pathway (JAK2, STAT5B, SOCS2, and PIK3CB) genes were selected for genotyping. The GHR exon 3-deleted/full-length (d3/fl) polymorphism was analyzed using tagSNP rs6873545.
  
  
  RESULTS
  After 1 week of GH replacement, homozygotes of the fl-GHR showed a better IGF1 response to GH than carriers of the d3-GHR (P=0.016). Conversely, homozygotes of the minor allele of PIK3CB SNP rs361072 responded better than carriers of the major allele (P=0.025). Compared with baseline, both SNPs were associated with the IGF1 response at 6 months (P=0.041 and P=0.047 respectively), and SNP rs6873545 was further associated with the IGF1 response at 1 year (P=0.041).
  
  
  CONCLUSIONS
  Our results indicate that common genetic variants in the GH signaling pathway may be of functional relevance to the response to GH replacement in GHD adults.
authors.affiliation: Department of Endocrinology, The Sahlgrenska Academy, University of Gothenburg, Gröna Stråket 8, Vita Stråket 15, SE-413 45 Göteborg, Sweden.
authors.forename: Camilla A M
authors.initials: CA
authors.lastname: Glad
authors.forename: Edna J L
authors.initials: EJ
authors.lastname: Barbosa
authors.forename: Helena
authors.initials: H
authors.lastname: Filipsson Nyström
authors.forename: Lena M S
authors.initials: LM
authors.lastname: Carlsson
authors.forename: Staffan
authors.initials: S
authors.lastname: Nilsson
authors.forename: Anna G
authors.initials: AG
authors.lastname: Nilsson
authors.forename: Per-Arne
authors.initials: PA
authors.lastname: Svensson
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Johannsson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D058534:Class I Phosphatidylinositol 3-Kinases; D015331:Cohort Studies; D016903:Drug Monitoring; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D013548:Sweden; D055815:Young Adult
chemical_list: C583557:IGF1 protein, human; D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C497132:PIK3CB protein, human