BclI Glucocorticoid Receptor Polymorphism Is Associated With Greater Body Fatness: The Hoorn and CODAM Studies

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 = 2.3 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