Heterozygosity for a mutation in the growth hormone-releasing hormone receptor gene does not influence adult stature, but affects body composition.
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.
Pereira
Rossana M C
RM
Division of Endocrinology, Johns Hopkins University, Baltimore, MD 21287, USA.
Aguiar-Oliveira
Manuel H
MH
Sagazio
Alessia
A
Oliveira
Carla R P
CR
Oliveira
Francielle T
FT
Campos
Viviane C
VC
Farias
Catarine T
CT
Vicente
Tábita A R
TA
Gois
Miburge B
MB
Oliveira
Joselina L M
JL
Marques-Santos
Celi
C
Rocha
Ivina E S
IE
Barreto-Filho
José A S
JA
Salvatori
Roberto
R
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*
D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D007334:Insulin-Like Growth Factor I; C048250:somatotropin releasing hormone receptor