Glucocorticoid receptor Bcl I variant is associated with an increased atherogenic profile in response to long-term overfeeding

The effect of the glucocorticoid receptor (GRL) gene Bcl I polymorphism on body composition and metabolic changes in response to overfeeding was studi ed. Twenty-four men (mean age 21 +/- 2 years) who constituted 12 pairs of i dentical twins ate a 4.2 MJ/day energy surplus, 6 days a week, during a per iod of 100 days. The GRL Bcl I marker was identified by Southern Blot techn ique. Total body fat was assessed by hydrodensitometry and abdominal fat ar eas were measured by computed tomography. Fasting plasma glucose and insuli n during an oral glucose tolerance test (OGTT) were assayed. The insulin an d glucose areas were computed using the trapezoidal method. Triglyceride an d cholesterol concentrations in plasma and lipoprotein fractions were deter mined enzymatically. The results showed that overfeeding induced a greater increase in body weight (p = 0.002) in the 2.3/2.3 kb (n = 12) than in the 4.5/2.3 kb (n = 12) subjects. In addition, plasma levels of total (p = 0.00 7) and low-density lipoprotein (LDL) cholesterol (p = 0.003), as well as sy stolic blood pressure (p = 0.036) increased more in the 2.3/2.3 kb than in the 4.5/2.3 kb subjects. The 2.3/2.3 kb genotype was also associated with a greater increase in abdominal visceral fat (p = 0.040) compared to the 4.5 /2.3 kb genotype. In conclusion, 2.3/2.3 kb subjects of the GRL Bcl I polym orphism experience greater increases in body weight, blood pressure and cho lesterol levels as well as visceral fat than 4.5/2.3 kb subjects in respons e to overfeeding. These data suggest that overfeeding induces an atherogeni c profile in subjects who are homozygotes for the 2.3 kb allele. (C) 2001 E lsevier Science Ireland Ltd. All rights reserved.