Heterozygosity for a mutation in the growth hormone-releasing hormone receptor gene does not influence adult stature, but affects body composition.

Abstract

CONTEXT:

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: Rossana M C Pereira, Manuel H Aguiar-Oliveira, Alessia Sagazio, Carla R P Oliveira, Francielle T Oliveira, Viviane C Campos, Catarine T Farias, Tábita A R Vicente, Miburge B Gois Jr, Joselina L M Oliveira, Celi Marques-Santos, Ivina E S Rocha, José A S Barreto-Filho, Roberto Salvatori
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 92 Issue 6 Pg. 2353-7 (Jun 2007) ISSN: 0021-972X [Print] United States
• PMID: 17356054 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Neuropeptide
• Receptors, Pituitary Hormone-Regulating Hormone
• Insulin-Like Growth Factor I
• somatotropin releasing hormone receptor

Topics

• Adult
• Aged
• Aging
• Body Composition (genetics)
• Body Height (genetics)
• Body Mass Index
• Brazil
• Female
• Heterozygote
• Humans
• Insulin Resistance (genetics)
• Insulin-Like Growth Factor I (metabolism)
• Male
• Middle Aged
• Mutation
• Phenotype
• Receptors, Neuropeptide (genetics)
• Receptors, Pituitary Hormone-Regulating Hormone (genetics)