title: Exon 3-deleted/full-length growth hormone receptor polymorphism genotype frequencies in Spanish short small-for-gestational-age (SGA) children and adolescents (n = 247) and in an adult control population (n = 289) show increased fl/fl in short SGA.
abstract: BACKGROUND
  A polymorphism in the human GH receptor gene (d3/fl-GHR) resulting in genomic deletion of exon 3 has been associated with the degree of height increase in response to GH therapy.
  
  
  OBJECTIVE
  The objective of the study was to evaluate the frequencies of d3/fl-GHR polymorphism genotypes in control and short small-for-gestational-age (SGA) populations.
  
  
  METHODS
  An adult control population with heights normally distributed (ACPNH) between -2 and +2 sd score (SDS) and a short non-GH-deficient SGA child population were selected.
  
  
  METHODS
  Thirty Spanish hospitals participated in the selection of the short non-GH-deficient SGA children in the setting of a controlled, randomized trial, and one of these hospitals selected the ACPNH. CONTROLS AND PATIENTS: Two hundred eighty-nine adult subjects of both sexes constituted the ACPNH and 247 children and adolescents of both sexes the short SGA patients.
  
  
  METHODS
  Heights and weights were recorded in the ACPNH, and auxologic and biochemical data were recorded at each hospital for the SGA patients; d3/fl-GHR genotypes were determined and data analyzed in a single hospital.
  
  
  RESULTS
  In short SGA patients, d3/fl-GHR genotype frequencies were significantly different from those in ACPNH, with a higher frequency of fl/fl genotype (P < 0.0001). In ACPNH, a trend toward diminished d3/d3 genotype frequency was observed in the shortest height group (height <or=-1 SDS and >or=-2 SDS, n = 60).
  
  
  CONCLUSIONS
  Our data showed significant differences in the frequency distribution of the d3/fl-GHR genotypes between a normally distributed adult height population and short SGA children, with the biologically less active fl/fl genotype being almost twice as frequent in SGA patients. These data suggest that the d3/fl-GHR polymorphism might be considered among the factors that contribute to the phenotypic expression of growth.
authors.affiliation: Department of Pediatrics, Hospital Vall D'Hebron, Autonmous University, Barcelona, Spain. laudi@ir.vhebron.net
authors.forename: Laura
authors.initials: L
authors.lastname: Audí
authors.forename: Cristina
authors.initials: C
authors.lastname: Esteban
authors.forename: Antonio
authors.initials: A
authors.lastname: Carrascosa
authors.forename: Rosa
authors.initials: R
authors.lastname: Espadero
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pérez-Arroyo
authors.forename: Rosa
authors.initials: R
authors.lastname: Arjona
authors.forename: María
authors.initials: M
authors.lastname: Clemente
authors.forename: Hartmut
authors.initials: H
authors.lastname: Wollmann
authors.forename: Linda
authors.initials: L
authors.lastname: Fryklund
authors.forename: Luis A
authors.initials: LA
authors.lastname: Parodi
mesh_terms: D000293:Adolescent; D000328:Adult; D001827:Body Height / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D035061:Control Groups; D004393:Dwarfism, Pituitary / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D006130:Growth Disorders / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011986:Receptors, Somatotropin / Q000235:genetics*
chemical_list: D011986:Receptors, Somatotropin