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J Clin Endocrinol Metab. 2013 Mar;98(3):E595-9. doi: 10.1210/jc.2012-3442. Epub 2013 Feb 7.

BclI glucocorticoid receptor polymorphism is associated with greater body fatness: the Hoorn and CODAM studies.

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1
Department of Internal Medicine, Division of Endocrinology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.

Abstract

CONTEXT:

The BclI polymorphism in the glucocorticoid receptor (GR) gene is associated with enhanced glucocorticoid (GC) sensitivity.

OBJECTIVE:

Our objective was to investigate the association of the BclI polymorphism with body fatness and insulin resistance.

DESIGN AND SETTING:

We conducted an observational cohort study, combining data from 2 cohort studies enriched with individuals with impaired glucose metabolism and/or diabetes mellitus type 2 (DM2).

PATIENTS AND METHODS:

We examined 1228 participants (mean age 64.7 years, 45% women) from the Cohort Study on Diabetes and Atherosclerosis Maastricht (CODAM, n = 543) and the Hoorn Study (n = 685). Body mass index (BMI), waist and hip circumferences, and waist-to-hip ratio (WHR) were obtained; insulin resistance was estimated using the homeostasis model assessment for insulin resistance (HOMA2-IR).

RESULTS:

We identified 519 noncarriers (CC), 540 heterozygous (CG) carriers, and 169 homozygous (GG) carriers of the G-allele of the BclI polymorphism. Homozygous carriers had a higher BMI (28.9 vs 27.9 kg/m(2)) and waist (99.6 vs 97.2 cm) and hip (105.5 vs 103.2 cm) circumference compared with noncarriers, also after adjustment for age, sex, cohort, glucose tolerance, and lifestyle risk factors: β = 0.94 kg/m(2) (95% confidence interval, 0.24-1.63), β = 2.84 cm (0.95;4.73) and β = 2.38 cm (0.88-3.87), respectively. Similar results were obtained when comparing homozygous carriers with heterozygous carriers: β = 1.03 kg/m(2) (0.34-1.72), β = 2.20 cm (0.31-4.08) and β = 1.99 cm (0.51-3.48), respectively. There were no differences in WHR. Ln-HOMA2-IR was higher in GG carriers compared with CG carriers; 0.29 vs 0.17 [β = 0.09 (0.01-0.17)], but this effect was attenuated after adjustment for BMI [β = 0.04 (-0.04 to 0.11)].

CONCLUSION:

Homozygous carriers of the BclI polymorphism of the GR gene have significantly greater total body fatness, contributing to higher HOMA2-IR, compared with heterozygous carriers and noncarriers.

PMID:
23393177
DOI:
10.1210/jc.2012-3442
[Indexed for MEDLINE]
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