Endocrine Abstracts

Single nucleotide polymorphisms in the glucocorticoid receptor (GR) gene influence tissue sensitivity of GR. Several studies have shown different effects of BclI GR polymorphism on body composition and metabolic parameters. The objective of this study was to explore the effect of BclI GR polymorphism on the body composition and glucose metabolism. Biochemical tests and hormonal evaluation were performed in 106 consecutive women with adrenal incidentalomas (AIs). Non-diabetic patients underwent an oral glucose tolerance test with 75 g glucose. Body composition was measured with dual-energy X-ray absorptiometry. DNA was obtained from peripheral blood leucocytes. The polymorphism was detected using PCR, RFLP and DNA sequencing. We observed no differences in mean age (57±9.6 vs 56.5±11.8, P=0.823), percent of postmenopausal women (76% vs 7%, P=0.550), and prevalence of metabolic syndrome (31.9% vs 21.3%, P=0.158) between carriers of the C allele of BclI polymorphism and non-carriers. BclI carriers have lower prevalence of impaired glucose tolerance (2.6% vs 17.5%, P=0.031), type 2 diabetes mellitus (T2DM) (9.1% vs 26%, P=0.034), and reduced glucose area under the curve, the mean difference of 2.62 (95% CI, 1.11-4.14), P= 0.001. BclI carriers have a tendency towards lower lean body mass (41.7 ±6.9 vs 44.1±5.7, P=0.08) and a significantly higher percentage of legs fat (43.36±5.75 vs 39.84±7.6, P=0.020). BclI polymorphism was significantly associated with sum of legs fat mass (FM) percentage (β=0.327, P=0.048). Also, subjects with greater legs/trunk FM ratio had higher odds to be BclI carriers, OR 1.046 (95% CI, 0.046-23.565, P=0.045). Logistic regression analysis showed that presence of T2DM was significantly negatively correlated with BclI polymorphism after adjusting for possible confounding factors such as age, truncal FM, appendicular lean mass index, and legs fat sum (OR=0.158, 95%CI 0.031-0.806, P=0.027). BclI carriers predispose to increased legs fat mass and greater legs/trunk FM ratio indicating reduced sensitivity to GC, which could explain why some women with AIs preserve more gluteo-femoral subcutaneous adipose tissue with beneficial effects on glucose metabolism.