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 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. 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.

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Persistent URL dx.doi.org/10.1530/EJE-10-0718, hdl.handle.net/1765/28082
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Manenschijn, L., van den Akker, E.L.T., Ester, W.A., Leunissen, R.W.J., Willemsen, R.H., van Rossum, E.F.C., … Hokken-Koelega, A.C.S.. (2010). 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. European Journal of Endocrinology, 163(6), 911–918. doi:10.1530/EJE-10-0718