Abstract
BackgroundGlucocorticoids have an important role in early growth and development. Glucocorticoid receptor gene polymorphisms have been identified that contribute to the variability in glucocorticoid sensitivity. We examined whether these glucocorticoid receptor gene polymorphisms are associated with growth in fetal and early postnatal life.MethodsThis study was embedded in a population-based prospective cohort study from fetal life onwards. The studied glucocorticoid receptor gene polymorphisms included BclI (rs41423247), TthIIII (rs10052957), GR-9β (rs6198), N363S (rs6195) and R23K (rs6789 and6190). Fetal growth was assessed by ultrasounds in second and third trimester of pregnancy. Anthropometric measurements in early childhood were performed at birth and at the ages of 6, 14 and 24 months postnatally. Analyses focused on weight, length and head circumference. Analyses were based on 2,414 healthy, Caucasian children.ResultsGlucocorticoid receptor gene polymorphisms were not associated with fetal weight, birth weight and early postnatal weight. Also, no associations were found with length and head circumference. Neither were these polymorphisms associated with the risks of low birth weight or growth acceleration from birth to 24 months of age.ConclusionsWe found in a large population-based cohort no evidence for an effect of known glucocorticoid receptor gene polymorphisms on fetal and early postnatal growth characteristics. Further systematic searches for common genetic variants by means of genome-wide association studies will enable us to obtain a more complete understanding of what genes and polymorphisms are involved in growth in fetal life and infancy.
Highlights
Glucocorticoids have an important role in early growth and development
In our population-based prospective cohort study we showed that glucocorticoid receptor gene polymorphisms are not consistently associated with growth in fetal and early postnatal life
We hypothezised that genetic variants leading to increased glucocorticoid sensitivity are associated with fetal growth retardation and postnatal growth acceleration
Summary
Glucocorticoids have an important role in early growth and development. Glucocorticoid receptor gene polymorphisms have been identified that contribute to the variability in glucocorticoid sensitivity. Polymorphisms in the glucocorticoid receptor gene have been suggested to contribute to this difference in sensitivity and thereby to differences in growth, development and metabolism. These glucocorticoid receptor gene variants may explain part of the previously. The GR-9b polymorphism was found to be related to a decreased sensitivity to glucocorticoids, leading to an increased risk of cardiovascular disease [16] These results suggest that common functional variants of the glucocorticoid receptor gene may affect body composition. Some studies showed an increasing effect of genetic variants in the glucocorticoid receptor gene with advancing age [8,17], the effect of these glucocorticoid receptor gene polymorphisms might be stronger on anthropometric measures in early life than on body mass index in adult life, because of very limited life style influences
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