Top

Published in:

Open Access 01-12-2010 | Research article

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

Authors: Miranda JJ Geelhoed, Eric AP Steegers, Jan W Koper, Elisabeth FC van Rossum, Henriette A Moll, Hein Raat, Henning Tiemeier, Albert Hofman, Vincent WV Jaddoe

Published in: BMC Medical Genetics | Issue 1/2010

Abstract

Background

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. We examined whether these glucocorticoid receptor gene polymorphisms are associated with growth in fetal and early postnatal life.

Methods

This 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.

Results

Glucocorticoid 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.

Conclusions

We 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.

Available only for authorised users

Huizenga NA, Koper JW, de Lange P, Pols HA, Stolk RP, Grobbee DE, de Jong FH, Lamberts SW: Interperson variability but intraperson stability of baseline plasma cortisol concentrations, and its relation to feedback sensitivity of the hypothalamo-pituitary-adrenal axis to a low dose of dexamethasone in elderly individuals. The Journal of clinical endocrinology and metabolism. 1998, 83: 47-54. 10.1210/jc.83.1.47.PubMed

Gluckman PD, Hanson MA, Cooper C, Thornburg KL: Effect of in utero and early-life conditions on adult health and disease. The New England journal of medicine. 2008, 359: 61-73. 10.1056/NEJMra0708473.CrossRefPubMedPubMedCentral

Whincup PH, Kaye SJ, Owen CG, Huxley R, Cook DG, Anazawa S, Barrett-Connor E, Bhargava SK, Birgisdottir BE, Carlsson S, et al: Birth weight and risk of type 2 diabetes: a systematic review. Jama. 2008, 300: 2886-2897. 10.1001/jama.2008.886.CrossRefPubMed

van Rossum EF, Roks PH, de Jong FH, Brinkmann AO, Pols HA, Koper JW, Lamberts SW: Characterization of a promoter polymorphism in the glucocorticoid receptor gene and its relationship to three other polymorphisms. Clinical endocrinology. 2004, 61: 573-581. 10.1111/j.1365-2265.2004.02132.x.CrossRefPubMed

van Rossum EF, Lamberts SW: Polymorphisms in the glucocorticoid receptor gene and their associations with metabolic parameters and body composition. Recent Prog Horm Res. 2004, 59: 333-357. 10.1210/rp.59.1.333.CrossRefPubMed

Stevens A, Ray DW, Zeggini E, John S, Richards HL, Griffiths CE, Donn R: Glucocorticoid sensitivity is determined by a specific glucocorticoid receptor haplotype. The Journal of clinical endocrinology and metabolism. 2004, 89: 892-897. 10.1210/jc.2003-031235.CrossRefPubMed

van Rossum EF, Koper JW, Huizenga NA, Uitterlinden AG, Janssen JA, Brinkmann AO, Grobbee DE, de Jong FH, van Duyn CM, Pols HA, et al: A polymorphism in the glucocorticoid receptor gene, which decreases sensitivity to glucocorticoids in vivo, is associated with low insulin and cholesterol levels. Diabetes. 2002, 51: 3128-3134. 10.2337/diabetes.51.10.3128.CrossRefPubMed

Finken MJ, Meulenbelt I, Dekker FW, Frolich M, Romijn JA, Slagboom PE, Wit JM: The 23K variant of the R23K polymorphism in the glucocorticoid receptor gene protects against postnatal growth failure and insulin resistance after preterm birth. The Journal of clinical endocrinology and metabolism. 2007, 92: 4777-4782. 10.1210/jc.2007-1290.CrossRefPubMed

Huizenga NA, Koper JW, De Lange P, Pols HA, Stolk RP, Burger H, Grobbee DE, Brinkmann AO, De Jong FH, Lamberts SW: A polymorphism in the glucocorticoid receptor gene may be associated with and increased sensitivity to glucocorticoids in vivo. The Journal of clinical endocrinology and metabolism. 1998, 83: 144-151. 10.1210/jc.83.1.144.PubMed

10.

van Rossum EF, Koper JW, Beld van den AW, Uitterlinden AG, Arp P, Ester W, Janssen JA, Brinkmann AO, de Jong FH, Grobbee DE, et al: Identification of the BclI polymorphism in the glucocorticoid receptor gene: association with sensitivity to glucocorticoids in vivo and body mass index. Clinical endocrinology. 2003, 59: 585-592. 10.1046/j.1365-2265.2003.01888.x.CrossRefPubMed

11.

Rosmond R, Chagnon YC, Holm G, Chagnon M, Perusse L, Lindell K, Carlsson B, Bouchard C, Bjorntorp P: A glucocorticoid receptor gene marker is associated with abdominal obesity, leptin, and dysregulation of the hypothalamic-pituitary-adrenal axis. Obesity research. 2000, 8: 211-218. 10.1038/oby.2000.24.CrossRefPubMed

12.

Marti A, Ochoa MC, Sanchez-Villegas A, Martinez JA, Martinez-Gonzalez MA, Hebebrand J, Hinney A, Vedder H: Meta-analysis on the effect of the N363S polymorphism of the glucocorticoid receptor gene (GRL) on human obesity. BMC Med Genet. 2006, 7: 50-10.1186/1471-2350-7-50.CrossRefPubMedPubMedCentral

13.

Buemann B, Vohl MC, Chagnon M, Chagnon YC, Gagnon J, Perusse L, Dionne F, Despres JP, Tremblay A, Nadeau A, et al: Abdominal visceral fat is associated with a BclI restriction fragment length polymorphism at the glucocorticoid receptor gene locus. Obesity research. 1997, 5: 186-192.CrossRefPubMed

14.

Rosmond R, Bouchard C, Bjorntorp P: Tsp509I polymorphism in exon 2 of the glucocorticoid receptor gene in relation to obesity and cortisol secretion: cohort study. BMJ. 2001, 322: 652-653. 10.1136/bmj.322.7287.652.CrossRefPubMedPubMedCentral

15.

Rosmond R, Chagnon YC, Chagnon M, Perusse L, Bouchard C, Bjorntorp P: A polymorphism of the 5'-flanking region of the glucocorticoid receptor gene locus is associated with basal cortisol secretion in men. Metabolism: clinical and experimental. 2000, 49: 1197-1199.CrossRef

16.

Akker van den EL, Koper JW, van Rossum EF, Dekker MJ, Russcher H, de Jong FH, Uitterlinden AG, Hofman A, Pols HA, Witteman JC, et al: Glucocorticoid receptor gene and risk of cardiovascular disease. Arch Intern Med. 2008, 168: 33-39. 10.1001/archinternmed.2007.41.CrossRefPubMed

17.

van Rossum EF, Voorhoeve PG, te Velde SJ, Koper JW, Delemarre-van de Waal HA, Kemper HC, Lamberts SW: The ER22/23EK polymorphism in the glucocorticoid receptor gene is associated with a beneficial body composition and muscle strength in young adults. The Journal of clinical endocrinology and metabolism. 2004, 89: 4004-4009. 10.1210/jc.2003-031422.CrossRefPubMed

18.

Jaddoe VW, Bakker R, van Duijn CM, Heijden van der AJ, Lindemans J, Mackenbach JP, Moll HA, Steegers EA, Tiemeier H, Uitterlinden AG, et al: The Generation R Study Biobank: a resource for epidemiological studies in children and their parents. Eur J Epidemiol. 2007, 22: 917-923. 10.1007/s10654-007-9209-z.CrossRefPubMedPubMedCentral

19.

Jaddoe VW, van Duijn CM, Heijden van der AJ, Mackenbach JP, Moll HA, Steegers EA, Tiemeier H, Uitterlinden AG, Verhulst FC, Hofman A: The Generation R Study: design and cohort update until the age of 4 years. Eur J Epidemiol. 2008, 23: 801-811. 10.1007/s10654-008-9309-4.CrossRefPubMed

20.

Rautanen A, Eriksson JG, Kere J, Andersson S, Osmond C, Tienari P, Sairanen H, Barker DJ, Phillips DI, Forsen T, et al: Associations of body size at birth with late-life cortisol concentrations and glucose tolerance are modified by haplotypes of the glucocorticoid receptor gene. The Journal of clinical endocrinology and metabolism. 2006, 91: 4544-4551. 10.1210/jc.2006-1065.CrossRefPubMed

21.

Stephens M, Smith NJ, Donnelly P: A new statistical method for haplotype reconstruction from population data. Am J Hum Genet. 2001, 68: 978-989. 10.1086/319501.CrossRefPubMedPubMedCentral

22.

Verburg BO, Steegers EA, De Ridder M, Snijders RJ, Smith E, Hofman A, Moll HA, Jaddoe VW, Witteman JC: New charts for ultrasound dating of pregnancy and assessment of fetal growth: longitudinal data from a population-based cohort study. Ultrasound Obstet Gynecol. 2008, 31: 388-396. 10.1002/uog.5225.CrossRefPubMed

23.

Hadlock FP, Deter RL, Harrist RB, Park SK: Fetal abdominal circumference as a predictor of menstrual age. Ajr. 1982, 139: 367-370.CrossRefPubMed

24.

Hadlock FP, Harrist RB, Deter RL, Park SK: Fetal femur length as a predictor of menstrual age: sonographically measured. Ajr. 1982, 138: 875-878.CrossRefPubMed

25.

Shepard M, Filly RA: A standardized plane for biparietal diameter measurement. J Ultrasound Med. 1982, 1: 145-150.PubMed

26.

Hadlock FP, Harrist RB, Carpenter RJ, Deter RL, Park SK: Sonographic estimation of fetal weight. The value of femur length in addition to head and abdomen measurements. Radiology. 1984, 150: 535-540.CrossRefPubMed

27.

Goldstein H, Browne W, Rasbash J: Multilevel modelling of medical data. Stat Med. 2002, 21: 3291-3315. 10.1002/sim.1264.CrossRefPubMed

28.

Littell RC, Henry PR, Ammerman CB: Statistical analysis of repeated measures data using SAS procedures. J Anim Sci. 1998, 76: 1216-1231.PubMed

29.

Ong KK, Ahmed ML, Emmett PM, Preece MA, Dunger DB: Association between postnatal catch-up growth and obesity in childhood: prospective cohort study. BMJ. 2000, 320: 967-971. 10.1136/bmj.320.7240.967.CrossRefPubMedPubMedCentral

30.

Benediktsson R, Lindsay RS, Noble J, Seckl JR, Edwards CR: Glucocorticoid exposure in utero: new model for adult hypertension. Lancet. 1993, 341: 339-341. 10.1016/0140-6736(93)90138-7.CrossRefPubMed

31.

Kajantie E, Dunkel L, Turpeinen U, Stenman UH, Wood PJ, Nuutila M, Andersson S: Placental 11 beta-hydroxysteroid dehydrogenase-2 and fetal cortisol/cortisone shuttle in small preterm infants. The Journal of clinical endocrinology and metabolism. 2003, 88: 493-500. 10.1210/jc.2002-021378.CrossRefPubMed

32.

Barker DJ, Bull AR, Osmond C, Simmonds SJ: Fetal and placental size and risk of hypertension in adult life. BMJ. 1990, 301: 259-262. 10.1136/bmj.301.6746.259.CrossRefPubMedPubMedCentral

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/11/39/prepub

Title: Glucocorticoid receptor gene polymorphisms do not affect growth in fetal and early postnatal life. The Generation R Study
Authors: Miranda JJ Geelhoed
Eric AP Steegers
Jan W Koper
Elisabeth FC van Rossum
Henriette A Moll
Hein Raat
Henning Tiemeier
Albert Hofman
Vincent WV Jaddoe
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2010
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/1471-2350-11-39

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2010

Do consanguineous parents of a child affected by an autosomal recessive disease have more DNA identical-by-descent than similarly-related parents with healthy offspring? Design of a case-control study

Mutations in epidermal growth factor receptor and K-ras in Chinese patients with colorectal cancer

SLC2A10 genetic polymorphism predicts development of peripheral arterial disease in patients with type 2 diabetes. SLC2A10and PAD in type 2 diabetes

Suggestive evidence of associations between liver X receptor β polymorphisms with type 2 diabetes mellitus and obesity in three cohort studies: HUNT2 (Norway), MONICA (France) and HELENA (Europe)

Effect of the rs2259816 polymorphism in the HNF1A gene on circulating levels of c-reactive protein and coronary artery disease (the ludwigshafen risk and cardiovascular health study)

Toll-like receptor gene polymorphisms are associated with susceptibility to graves' ophthalmopathy in Taiwan males