title: Heterozygosity for a mutation in the growth hormone-releasing hormone receptor gene does not influence adult stature, but affects body composition.
abstract: BACKGROUND
  Biallelic mutations in the GHRH receptor (GHRHR) gene (GHRHR) are a frequent cause of isolated GH deficiency (IGHD). Although heterozygous carriers of these mutations appear normal, we hypothesized that heterozygosity for a GHRHR mutation might be associated with a subclinical phenotype.
  
  
  METHODS
  We studied members of a large Brazilian kindred with IGHD (Itabaianinha cohort) caused by a homozygous null GHRHR mutation. We compared 76 adult subjects (age, 25-75 yr) heterozygous for the mutation (WT/MT) with 77 sex-matched controls from the same population who are homozygous for the wild-type GHRHR allele (WT/WT).
  
  
  RESULTS
  We found no difference in adult height and sd score for serum IGF-I between the two groups. Body weight, body mass index, skin folds, waist and hip circumferences, and lean mass were all reduced in WT/MT subjects. Percentage fat mass and waist/hip ratio were similar in the two groups. Fasting insulin and homeostasis model assessment of insulin resistance were lower in WT/MT. The other biochemical parameters [total and fractionated cholesterol, triglycerides, lipoprotein (a), and C-reactive protein] were not different between the two groups.
  
  
  CONCLUSIONS
  Heterozygosity for a null GHRHR mutation is not associated with reduction in adult stature or in serum IGF-I but is associated with changes in body composition and possibly an increase in insulin sensitivity. These effects do not seem to be modulated by changes in circulating IGF-I.
authors.affiliation: Division of Endocrinology, Johns Hopkins University, Baltimore, MD 21287, USA.
authors.forename: Rossana M C
authors.initials: RM
authors.lastname: Pereira
authors.forename: Manuel H
authors.initials: MH
authors.lastname: Aguiar-Oliveira
authors.forename: Alessia
authors.initials: A
authors.lastname: Sagazio
authors.forename: Carla R P
authors.initials: CR
authors.lastname: Oliveira
authors.forename: Francielle T
authors.initials: FT
authors.lastname: Oliveira
authors.forename: Viviane C
authors.initials: VC
authors.lastname: Campos
authors.forename: Catarine T
authors.initials: CT
authors.lastname: Farias
authors.forename: Tábita A R
authors.initials: TA
authors.lastname: Vicente
authors.forename: Miburge B
authors.initials: MB
authors.lastname: Gois
authors.forename: Joselina L M
authors.initials: JL
authors.lastname: Oliveira
authors.forename: Celi
authors.initials: C
authors.lastname: Marques-Santos
authors.forename: Ivina E S
authors.initials: IE
authors.lastname: Rocha
authors.forename: José A S
authors.initials: JA
authors.lastname: Barreto-Filho
authors.forename: Roberto
authors.initials: R
authors.lastname: Salvatori
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging; D001823:Body Composition / Q000235:genetics*; D001827:Body Height / Q000235:genetics*; D015992:Body Mass Index; D001938:Brazil; D005260:Female; D006579:Heterozygote; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D018013:Receptors, Neuropeptide / Q000235:genetics*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics*
chemical_list: D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D007334:Insulin-Like Growth Factor I; C048250:somatotropin releasing hormone receptor