Glucocorticoid receptor gene polymorphisms do not affect growth in fetal and early postnatal life. The Generation R Study

Geelhoed, Miranda; Steegers, Eric A.P.; Koper, Jan W.; Rossum, Elisabeth F.C. van; Moll, Henriëtte A.; Raat, Hein; Tiemeier, Henning; Hofman, Albert; Jaddoe, Vincent W.V.

doi:10.1186/1471-2350-11-39

Cited by 14 publications

(12 citation statements)

References 32 publications

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“…We studied a large group of SGA subjects and did not find an association between the haplotype 3, which includes the Bcl1 polymorphism, and size at birth corrected for gestational age. This is in line with the results published by Geelhoed et al (21). They showed that in a large population-based cohort, GR polymorphisms were not associated with birth Data are expressed as means, P value was calculated using ANCOVA; data are adjusted for age and gender; 0, noncarriers; 1, heterozygous and homozygous carriers; n, number of SGA subjects.…”

Section: Discussionsupporting

confidence: 79%

“…weight, birth length, and postnatal growth (21). Interestingly, we found an association between heterozygous carriers of haplotype 4, characterized by the 9b polymorphism and lower birth weight corrected for gestational age.…”

Section: Discussionmentioning

confidence: 59%

“…However, the minor allele of this polymorphism has the highest minor allele frequency. This suggests that a considerable part of the variation in the GR gene is covered by the haplotypes that we have constructed (21). The GR gene and haplotypes are shown in Fig.…”

Section: Genetic Analysismentioning

confidence: 97%

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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

Manenschijn

Akker²,

Ester³

et al. 2010

European Journal of Endocrinology

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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.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 59%

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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

Manenschijn

Akker²,

Ester³

et al. 2010

European Journal of Endocrinology

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“…Also, strategies for genetic scoring analyses are being developed to estimate predictive values of identified genetic variants [171,172]. Although a GWAS is available in children, we use DNA from both children and parents for genotyping for candidate gene or replication studies [173][174][175][176][177][178][179][180][181][182]. Missing data in DNA samples in children will be collected by blood sampling or other methods at follow-up measurements.…”

Section: Biological Samplesmentioning

confidence: 99%

The Generation R Study: design and cohort update 2012

et al. 2012

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The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health during fetal life, childhood and adulthood. The study focuses on four primary areas of research: (1) growth and physical development; (2) behavioural and cognitive development; (3) diseases in childhood; and (4) health and healthcare for pregnant women and children. In total, 9,778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. General follow-up rates until the age of 4 years exceed 75%. Data collection in mothers, fathers and preschool children included questionnaires, detailed physical and ultrasound examinations, behavioural observations, and biological samples. A genome wide association screen is available in the participating children. Regular detailed hands on assessment are performed from the age of 5 years onwards. Eventually, results forthcoming from the Generation R Study have to contribute to the development of strategies for optimizing health and healthcare for pregnant women and children.

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“…Polymorphic markers of the mineralocorticoid receptor (-2G>C [rs2070951] and I180V [rs5522]) were assessed as described by Klok et al [30]. Two polymorphisms (NR3C1-1 [rs10482605] and N363S [rs6195]) located within the glucocorticoid receptor gene were analyzed as described by Geelhoed et al [31]. Individual genotypes were determined using the SDS software (version 2.3, Applied Biosystems).…”

Section: Dna Analysismentioning

confidence: 99%

Common variants of the mineralocorticoid and glucocorticoid receptor genes may contribute to pregnancy-related anxiety: a pilot study

2012

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AbstractThe hypothalamic-pituitary-adrenal (HPA) axis overactivity is thought to contribute to increased vulnerability to maternal stress. We hypothesize that functionally relevant polymorphic variants of the glucocorticoid (NR3C1) and mineralocorticoid (NR3C2) receptor genes mediating biological effects of cortisol, a major stress hormone, could also modulate the capacity to cope with pregnancy-related anxiety. Genomic DNA from the blood of 42 women with pregnancy-related anxiety and 42 age-matched women with normal pregnancy (5–6th months of gestation) were genotyped for markers rs6195 and rs10482605 of NR3C1 and two NR3C2 polymorphisms (rs5522 and rs2070951) using a Taqman allele discrimination assay. Serum total cortisol was measured using an ELISA technique. The allele Ser363 of rs6195 (the N363S polymorphism of NR3C1) was found to be associated with a higher risk of maternal stress (odds ratio (OR)=5.27; P=0.001). For NR3C2, the allele Val180 of rs5522 (I180V) also showed association with increased risk of neonatal stress (OR=1.97; P=0.038). Both predisposing gene variants were also associated with significantly elevated levels of cortisol in normally pregnant women and females with pregnancy-related anxiety. Our results suggest that pregnancy-related anxiety can be modulated by variants of NR3C1 and NR3C2 associated with increased basal cortisol levels. Thus, our findings provide evidence in support of the suggestion that elevated cortisol levels and HPA axis hyperactivity are implicated in pregnancy-related anxiety.

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Glucocorticoid receptor gene polymorphisms do not affect growth in fetal and early postnatal life. The Generation R Study

Cited by 14 publications

References 32 publications

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

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

The Generation R Study: design and cohort update 2012

Common variants of the mineralocorticoid and glucocorticoid receptor genes may contribute to pregnancy-related anxiety: a pilot study

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