title: Genetic polymorphisms in the locus control region and promoter of GH1 are related to serum IGF-I levels and height in patients with isolated growth hormone deficiency and healthy controls.
abstract: OBJECTIVE
  Expression of the human growth hormone (GH) gene (GH1) is regulated by a locus control region (LCR) and the highly polymorphic GH1 promoter. We analyzed GH1 LCR/promoter single nucleotide polymorphisms (SNPs) in patients with isolated growth hormone deficiency (IGHD) in relation to clinical data.
  
  
  METHODS
  We directly sequenced the GH1 LCR/promoter of 62 Dutch IGHD patients without mutations or deletions in GH1 or GHRHR and of 72 controls with normal height. We related GH1 LCR/promoter SNPs to height, serum insulin-like growth factor 1 (IGF-I) levels and response to GH treatment.
  
  
  RESULTS
  In IGHD patients, promoter SNPs 6, 8 and 9 were associated with height and IGF-1 levels. In controls, SNPs 6 and 11 were associated with height. Homozygosity for the minor allele of SNP 9, associated with lower IGF-I levels in patients, was significantly more frequent among patients than among controls. Genotypes based on SNPs 6, 8, 9 and 11 explained 10.8% of IGF-I SDS variation in IGHD patients and 15.9% of height SDS variation in controls.
  
  
  CONCLUSIONS
  GH1 Promoter SNPs 6, 8 and 9 were associated with height and IGF-1 levels among patients, and SNPs 6 and 11 with height in controls.
authors.affiliation: Department of Pediatrics, Division of Endocrinology, Sophia Children's Hospital, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Laura C G
authors.initials: LC
authors.lastname: de Graaff
authors.forename: Jesus
authors.initials: J
authors.lastname: Argente
authors.forename: Joyce B J
authors.initials: JB
authors.lastname: van Meurs
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Anita C S
authors.initials: AC
authors.lastname: Hokken-Koelega
mesh_terms: D000293:Adolescent; D000328:Adult; D001827:Body Height / Q000235:genetics* / Q000502:physiology; D016022:Case-Control Studies; D002648:Child; D004393:Dwarfism, Pituitary / Q000097:blood* / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006262:Health; D019382:Human Growth Hormone / Q000235:genetics*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism*; D015810:Linkage Disequilibrium; D019901:Locus Control Region / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I