Glucocorticoid receptor gene haplotypes are not associated with birth anthropometry, blood pressure, glucose and insulin concentrations, and body composition in subjects born small for gestational age.
OBJECTIVE
Smaller size at birth has been associated with an increased risk of metabolic and cardiovascular disorders in adult life. Fetal programming of the hypothalamic-pituitary-adrenal axis has been suggested as a possible explanation. Fetal glucocorticoid (GC) overexposure has effects that suggest a role of GCs in this programming. The effects of GCs are mediated through the GC receptor (GR or NR3C1). Several functional polymorphisms have been described, which are associated with relative GC resistance or hypersensitivity. Our aim is to compare frequencies of GR haplotypes, characterized by the R23K, N363S, Bcl1, or 9β polymorphisms, in subjects born small for gestational age (SGA) and associate birth anthropometry data, response to GH treatment, blood pressure, glucose and insulin concentrations, and body composition with these haplotypes.


METHODS
In total, 418 SGA subjects and 697 healthy controls were enrolled in this study. Methods Anthropometry data were obtained, as well as blood samples to determine fasting glucose and insulin concentrations. Dual energy X-ray absorptiometry scans were used to measure the amount of fat and lean mass.


RESULTS
No differences were found between GR haplotype frequencies in SGA children compared with healthy controls. No associations were found between GR haplotypes and birth length and birth weight, growth response during GH treatment, blood pressure, glucose and insulin concentrations, and body composition.


CONCLUSIONS
GR haplotypes and their effect on GC sensitivity do not seem to play a significant role in GH-induced catch-up growth and the risk factors of developing metabolic and cardiovascular disorders in adult life of SGA children.
Manenschijn
L
L
Subdivision of Endocrinology, Department of Internal Medicine, Erasmus Medical Center and Sophia Children's Hospital, Rotterdam, The Netherlands. l.manenschijn@erasmusmc.nl
van den Akker
E L T
EL
Ester
W A
WA
Leunissen
R W J
RW
Willemsen
R H
RH
van Rossum
E F C
EF
Koper
J W
JW
Lamberts
S W J
SW
Hokken-Koelega
A C S
AC
D000328:Adult; D001724:Birth Weight; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000235:genetics; D001823:Body Composition / Q000235:genetics*; D002318:Cardiovascular Diseases; D002648:Child; D005260:Female; D005787:Gene Frequency; D005938:Glucocorticoids / Q000494:pharmacology; D013006:Growth Hormone / Q000627:therapeutic use; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000254:growth & development*; D007328:Insulin / Q000097:blood; D008297:Male; D011110:Polymorphism, Genetic; D011965:Receptors, Glucocorticoid / Q000235:genetics*
D001786:Blood Glucose; D005938:Glucocorticoids; D007328:Insulin; C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid; D013006:Growth Hormone