TY - JOUR
T1 - Heterozygosity for a mutation in the growth hormone-releasing hormone receptor gene does not influence adult stature, but affects body composition
AU - Pereira, Rossana M.C.
AU - Aguiar-Oliveira, Manuel H.
AU - Sagazio, Alessia
AU - Oliveira, Carla R.P.
AU - Oliveira, Francielle T.
AU - Campos, Viviane C.
AU - Farias, Catarine T.
AU - Vicente, Tábita A.R.
AU - Gois, Miburge B.
AU - Oliveira, Joselina L.M.
AU - Marques-Santos, Celi
AU - Rocha, Ívina E.S.
AU - Barreto-Filho, José A.S.
AU - Salvatori, Roberto
N1 - Funding Information:
This work was supported by National Institutes of Health Grant 1 R01 DK065718 and by a grant from the Genentech Center for Clinical Research in Endocrinology (both to R.S.).
Funding Information:
Disclosure Statement: R.M.C.P., M.H.A.-O., A.S., C.R.P.O., F.T.O., V.C.C., C.T.F., T.A.R.V., M.B.G., J.L.M.O., C.M.-S., I.E.S.R, and J.A.S.B.-F. have nothing to declare. R.S. receives grant support from Genentech (8/1/04-7/31/08).
PY - 2007/6
Y1 - 2007/6
N2 - 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.
AB - 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.
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U2 - 10.1210/jc.2007-0092
DO - 10.1210/jc.2007-0092
M3 - Article
C2 - 17356054
AN - SCOPUS:34347243206
SN - 0021-972X
VL - 92
SP - 2353
EP - 2357
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 6
ER -