TY - JOUR
T1 - BclI Glucocorticoid Receptor Polymorphism Is Associated With Greater Body Fatness: The Hoorn and CODAM Studies
AU - Geelen, C.C.
AU - van Greevenbroek, M.M.
AU - van Rossum, E.F.
AU - Schaper, N.C.
AU - Nijpels, G.
AU - 't Hart, L.M.
AU - Schalkwijk, C.G.
AU - Ferreira, I.
AU - van der Kallen, C.J.
AU - Sauerwein, H.P.
AU - Dekker, J.M.
AU - Stehouwer, C.D.
AU - Havekes, B.
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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: beta = 0.94 kg/m(2) (95% confidence interval, 0.24-1.63), beta = 2.84 cm (0.95; 4.73) and beta = 2.38 cm (0.88-3.87), respectively. Similar results were obtained when comparing homozygous carriers with heterozygous carriers: beta = 1.03 kg/m(2) (0.34-1.72), beta = 2.20 cm (0.31-4.08) and beta = 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 [beta = 0.09 (0.01-0.17)], but this effect was attenuated after adjustment for BMI [beta = 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. (J Clin Endocrinol Metab 98: E595-E599, 2013)
AB - 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: beta = 0.94 kg/m(2) (95% confidence interval, 0.24-1.63), beta = 2.84 cm (0.95; 4.73) and beta = 2.38 cm (0.88-3.87), respectively. Similar results were obtained when comparing homozygous carriers with heterozygous carriers: beta = 1.03 kg/m(2) (0.34-1.72), beta = 2.20 cm (0.31-4.08) and beta = 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 [beta = 0.09 (0.01-0.17)], but this effect was attenuated after adjustment for BMI [beta = 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. (J Clin Endocrinol Metab 98: E595-E599, 2013)
U2 - 10.1210/jc.2012-3442
DO - 10.1210/jc.2012-3442
M3 - Article
C2 - 23393177
SN - 0021-972X
VL - 98
SP - E595-E599
JO - Journal of Clinical Endocrinology & Metabolism
JF - Journal of Clinical Endocrinology & Metabolism
IS - 3
ER -