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

Abstract

Objective: Smaller size at birth has been associated with an increased risk of metabolic and cardiovascular disorders in adult life. Fetal programing 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 programing. 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 9b 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. Design: 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. Conclusion: 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.

Glucocorticoid Receptor Gene Variants and Neonatal Outcome in Very-Low-Birth-Weight Preterm Infants

“…In our cohort, we detected an association between N363S and blood pressure; however, it disappeared in the pure carrier analysis after excluding any compound heterozygotes and carriers of BclI and R23K . This is in line with findings of other pediatric and adult studies, which did not detect an association of N363S and blood pressure later in life [6,24,25]. …”

Long-term glucocorticoid concentrations as a risk factor for childhood obesity and adverse body-fat distribution

“…A different study, although very early in life, assessing the association between GR gene SNPs with growth characteristics in neonates, did not report a significant effect of differential GR gene SNPs. 33,41 Additionally, in the current study no associations with GR gene SNPs and longterm glucocorticoid concentrations were found. This is the first study to assess the association between scalp-hair glucocorticoids and GR polymorphisms.…”

NR3C1 gene polymorphism for genetic susceptibility to infantile spasms in a Chinese population

“…GR-mediated genomic events can occur as a result of stress or GC overexposure (van den Akker et al, 2009). Previous studies have shown that polymorphisms in the coding and regulatory regions of NR3C1 are associated with the onset of some Life Sciences 91 (2012) 37-43 diseases (such as major depression, bipolar disorder, alcohol abuse, and others) and the response to GC (Bouma et al, 2011;Desrivieres et al, 2011;Manenschijn et al, 2010;. However, whether genetic variants of NR3C1 are associated with IS has not been fully researched.…”