ABDOMINAL VISCERAL FAT IS ASSOCIATED WITH A BCLI RESTRICTION-FRAGMENT-LENGTH-POLYMORPHISM AT THE GLUCOCORTICOID RECEPTOR GENE LOCUS

Several investigations have suggested that body fat distribution is in fluenced by nonpathologic variations in the responsiveness to cortisol . Genetic variations in the glucocorticoid receptor (GRL) could theref ore potentially have an impact an I-he level of abdominal fat. A restr iction fragment length polymorphism (RFLP) has previously been detecte d with the BclI restriction enzyme in the GRL gene identifying two all eles with fragment lengths of 4.5 and 2.3 kb. This study investigates whether abdominal fat areas measured by computerized tomography (CT) a re associated with this polymorphism in 152 middle-aged men and women. The less frequent 4.5-kb allele was found to be associated with a hig her abdominal visceral fat (AVF) area independently of total body fat mass (4.5/4.5 vs. 2.3/2.3 kb genotype; men: 190.7 +/- 30.1 vs. 150.7 /- 33.3 cm(2), p=0.04; women: 132.7 +/- 37.3 vs. 101.3 +/- 34.5 cm(2), p=0.06). However, the association with AVF was seen only in subjects of the lower tertile of the percent body fat level, In these subjects, the polymorphism was found to account for 41% (p=0.003) and 35% (p=0. 007), in men and women, respectively, of the total variance in AVF are a. The consistent association between the GRL polymorphism detected wi th BclI and AVF area suggests that this gene or a locus in linkage dis equilibrium with the BclI restriction site may contribute to the accum ulation of AVF.