Tags

Type your tag names separated by a space and hit enter

Associations of body size at birth with late-life cortisol concentrations and glucose tolerance are modified by haplotypes of the glucocorticoid receptor gene.
J Clin Endocrinol Metab. 2006 Nov; 91(11):4544-51.JC

Abstract

CONTEXT

Small body size at birth is associated with cardiovascular disease and type 2 diabetes in adult life. This link may be in part mediated by early-life programming of the hypothalamic-pituitary-adrenal axis (HPAA) function.

OBJECTIVE

Our objective was to assess whether haplotypes of the glucocorticoid receptor (GR) gene modify this link.

DESIGN AND PARTICIPANTS

We conducted a birth cohort study that included 437 men and women born in Helsinki, Finland, during 1924-1933, whose birth measurements were recorded.

MAIN OUTCOME MEASURES

We studied how the oral glucose tolerance test and fasting plasma total and free cortisol concentrations and, in a subset of 162 women, a more detailed HPAA evaluation, are predicted by body size at birth and haplotypes of the GR locus. We also measured the haplotype-specific relative mRNA expression level for the haplotype of interest.

RESULTS

One of the haplotypes was associated with lower birth weight and length and higher fasting plasma and mean 24-h salivary cortisol. Moreover, this haplotype modified the association of length at birth with adult phenotypes; in carriers, short length at birth was associated with increased fasting plasma cortisol, cortisol/corticosteroid-binding globulin ratio, impaired glucose tolerance or diabetes [1 cm decrease corresponded to 1.36-fold odds ratio; 95% confidence interval (CI), 1.09-1.70; P = 0.007], and higher 120-min glucose (5.8%; 95% CI, 2.5-9.1%; P = 0.0007), but no association was seen in noncarriers (P for interaction was 0.06, 0.01, 0.02, and 0.01, respectively). The mRNA expression level of this haplotype was 93.7% (95% CI, 90.5-96.8%; P = 2.2 x 10(-4)) of the expression level of the other haplotypes.

CONCLUSIONS

A common GR haplotype may contribute to and modify the association of short length at birth with adult glucose tolerance and HPAA function by a mechanism that affects regulation of GR expression.

Authors+Show Affiliations

Department of Medical Genetics, University of Helsinki, FIN-00014 Helsinki, Finland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16895953

Citation

Rautanen, Anna, 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, vol. 91, no. 11, 2006, pp. 4544-51.
Rautanen A, Eriksson JG, Kere J, 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. J Clin Endocrinol Metab. 2006;91(11):4544-51.
Rautanen, A., Eriksson, J. G., Kere, J., Andersson, S., Osmond, C., Tienari, P., Sairanen, H., Barker, D. J., Phillips, D. I., Forsén, T., & Kajantie, E. (2006). 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, 91(11), 4544-51.
Rautanen A, 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. J Clin Endocrinol Metab. 2006;91(11):4544-51. PubMed PMID: 16895953.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Associations of body size at birth with late-life cortisol concentrations and glucose tolerance are modified by haplotypes of the glucocorticoid receptor gene. AU - Rautanen,Anna, AU - Eriksson,Johan G, AU - Kere,Juha, AU - Andersson,Sture, AU - Osmond,Clive, AU - Tienari,Pentti, AU - Sairanen,Heikki, AU - Barker,David J P, AU - Phillips,David I W, AU - Forsén,Tom, AU - Kajantie,Eero, Y1 - 2006/08/08/ PY - 2006/8/10/pubmed PY - 2007/1/16/medline PY - 2006/8/10/entrez SP - 4544 EP - 51 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 91 IS - 11 N2 - CONTEXT: Small body size at birth is associated with cardiovascular disease and type 2 diabetes in adult life. This link may be in part mediated by early-life programming of the hypothalamic-pituitary-adrenal axis (HPAA) function. OBJECTIVE: Our objective was to assess whether haplotypes of the glucocorticoid receptor (GR) gene modify this link. DESIGN AND PARTICIPANTS: We conducted a birth cohort study that included 437 men and women born in Helsinki, Finland, during 1924-1933, whose birth measurements were recorded. MAIN OUTCOME MEASURES: We studied how the oral glucose tolerance test and fasting plasma total and free cortisol concentrations and, in a subset of 162 women, a more detailed HPAA evaluation, are predicted by body size at birth and haplotypes of the GR locus. We also measured the haplotype-specific relative mRNA expression level for the haplotype of interest. RESULTS: One of the haplotypes was associated with lower birth weight and length and higher fasting plasma and mean 24-h salivary cortisol. Moreover, this haplotype modified the association of length at birth with adult phenotypes; in carriers, short length at birth was associated with increased fasting plasma cortisol, cortisol/corticosteroid-binding globulin ratio, impaired glucose tolerance or diabetes [1 cm decrease corresponded to 1.36-fold odds ratio; 95% confidence interval (CI), 1.09-1.70; P = 0.007], and higher 120-min glucose (5.8%; 95% CI, 2.5-9.1%; P = 0.0007), but no association was seen in noncarriers (P for interaction was 0.06, 0.01, 0.02, and 0.01, respectively). The mRNA expression level of this haplotype was 93.7% (95% CI, 90.5-96.8%; P = 2.2 x 10(-4)) of the expression level of the other haplotypes. CONCLUSIONS: A common GR haplotype may contribute to and modify the association of short length at birth with adult glucose tolerance and HPAA function by a mechanism that affects regulation of GR expression. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/16895953/Associations_of_body_size_at_birth_with_late_life_cortisol_concentrations_and_glucose_tolerance_are_modified_by_haplotypes_of_the_glucocorticoid_receptor_gene_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2006-1065 DB - PRIME DP - Unbound Medicine ER -