title: Human growth hormone (GH1) gene polymorphism map in a normal-statured adult population.
abstract: OBJECTIVE
  GH1 gene presents a complex map of single nucleotide polymorphisms (SNPs) in the entire promoter, coding and noncoding regions. The aim of the study was to establish the complete map of GH1 gene SNPs in our control normal population and to analyse its association with adult height.
  
  
  METHODS
  A systematic GH1 gene analysis was designed in a control population of 307 adults of both sexes with height normally distributed within normal range for the same population: -2 standard deviation scores (SDS) to +2 SDS. An analysis was performed on individual and combined genotype associations with adult height.
  
  
  RESULTS
  Twenty-five SNPs presented a frequency over 1%: 11 in the promoter (P1 to P11), three in the 5'UTR region (P12 to P14), one in exon 1 (P15), three in intron 1 (P16 to P18), two in intron 2 (P19 and P20), two in exon 4 (P21 and P22) and three in intron 4 (P23 to P25). Twenty-nine additional changes with frequencies under 1% were found in 29 subjects. P8, P19, P20 and P25 had not been previously described. P6, P12, P17 and P25 accounted for 6.2% of the variation in adult height (P = 0.0007) in this population with genotypes A/G at P6, G/G at P6 and A/G at P12 decreasing height SDS (-0.063 +/- 0.031, -0.693 +/- 0.350 and -0.489 +/- 0.265, Mean +/- SE) and genotypes A/T at P17 and T/G at P25 increasing height SDS (+1.094 +/- 0.456 and +1.184 +/- 0.432).
  
  
  CONCLUSIONS
  This study established the GH1 gene sequence variation map in a normal adult height control population confirming the high density of SNPs in a relatively small gene. Our study shows that the more frequent SNPs did not significantly contribute to height determination, while only one promoter and two intronic SNPs contributed significantly to it. Studies in larger populations will have to confirm the associations and in vitro functional studies will elucidate the mechanisms involved. Systematic GH1 gene analysis in patients with growth delay and suspected GH deficiency/insufficiency will clarify whether different SNP frequencies and/or the presence of different sequence changes may be associated with phenotypes in them.
authors.affiliation: Department of Pediatrics and Pediatric Endocrinology, Hospital Materno-Infantil Vall d'Hebron, Autonomous University of Barcelona, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Esteban
authors.forename: Laura
authors.initials: L
authors.lastname: Audí
authors.forename: Antonio
authors.initials: A
authors.lastname: Carrascosa
authors.forename: Mónica
authors.initials: M
authors.lastname: Fernández-Cancio
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pérez-Arroyo
authors.forename: Angels
authors.initials: A
authors.lastname: Ulied
authors.forename: Pilar
authors.initials: P
authors.lastname: Andaluz
authors.forename: Rosa
authors.initials: R
authors.lastname: Arjona
authors.forename: Marian
authors.initials: M
authors.lastname: Albisu
authors.forename: María
authors.initials: M
authors.lastname: Clemente
authors.forename: Miquel
authors.initials: M
authors.lastname: Gussinyé
authors.forename: Diego
authors.initials: D
authors.lastname: Yeste
mesh_terms: D000328:Adult; D001483:Base Sequence; D001827:Body Height / Q000235:genetics*; D016009:Chi-Square Distribution; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D019382:Human Growth Hormone / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D016415:Sequence Alignment
chemical_list: D017931:DNA Primers; D019382:Human Growth Hormone