Impact of the growth hormone receptor exon 3 deletion gene polymorphism on glucose metabolism, lipids, and insulin-like growth factor-I levels during puberty.
BACKGROUND
The GH/IGF-I axis has major impact on insulin sensitivity and insulin secretion. Recently a polymorphism in the GH receptor gene (GHR), a genomic deletion of exon 3 (GHRd3), has been linked to increased responsiveness to GH.


OBJECTIVE
The objective of the present study was to evaluate the impact of the GHRd3 gene polymorphism on insulin sensitivity, insulin secretion, lipids, and IGF-I levels in healthy children and adolescents.


METHODS
This was cross-sectional and was part of the COPENHAGEN puberty study.


METHODS
The study was conducted at a tertiary center for pediatric endocrinology.


METHODS
Participants included 142 healthy Caucasian subjects (65 boys) aged 8.5-16.1 yr.


METHODS
Standard 2-h oral glucose tolerance tests were preformed. GHR genotypes were determined by multiplex PCR. Main outcome measures were insulin sensitivity, insulin secretion, serum lipids, and IGF-I levels.


RESULTS
Insulin secretion was higher in children and adolescents with a least one GHRd3 allele, even after adjustment for age, sex, pubertal stage, and insulin sensitivity (P = 0.018). Disposition index was higher in GHRd3-positive subjects (P = 0.026). In addition, the GHRd3 allele was associated with higher triglyceride (P = 0.028), but not IGF-I levels.


CONCLUSIONS
The presence of at least one GHRd3 allele was associated with higher insulin secretion for a given degree of insulin sensitivity in healthy children and adolescents during puberty. In addition, the presence of the GHRd3 allele was associated with a higher disposition index. Thus, this common polymorphism in the GHR gene might play a role for pancreatic beta-cell compensatory capacity.
Sørensen
Kaspar
K
Department of Growth and Reproduction, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen, Denmark. kaspar.soerensen@rh.regionh.dk
Aksglaede
Lise
L
Munch-Andersen
Thor
T
Aachmann-Andersen
Niels Jacob
NJ
Leffers
Henrik
H
Helge
Jørn Wulff
JW
Hilsted
Linda
L
Juul
Anders
A
D000293:Adolescent; D000483:Alleles; D002648:Child; D003430:Cross-Sectional Studies; D005091:Exons; D005260:Female; D017353:Gene Deletion; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male; D011110:Polymorphism, Genetic; D011627:Puberty / Q000235:genetics* / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000235:genetics*; D014280:Triglycerides / Q000097:blood*
D007328:Insulin; D011986:Receptors, Somatotropin; D014280:Triglycerides; D007334:Insulin-Like Growth Factor I; D005947:Glucose