Association of obesity, but not diabetes or hypertension, with glucocorticoid receptor N363S variant.

OBJECTIVE

To determine whether the N363S variant in the glucocorticoid receptor (encoded by nuclear receptor subfamily 3, group C, member 1: NR3C1) is associated with obesity, type 2 diabetes, or hypertension.

RESEARCH METHODS AND PROCEDURES

This was a cross-sectional case-control study involving 951 Anglo-Celtic/Northern European subjects from Sydney. This study consisted of the following: 1) an obesity clinic group, most of whom had "morbid obesity" (mean BMI for group = 43 +/- 8 kg/m(2); n = 152); 2) a type 2 diabetes clinic group (n = 356); 3) patients with essential hypertension who had a strong family history (n = 141); and 4) normal healthy controls (n = 302). N363S genotype, BMI, and a range of other parameters relevant to each group were measured.

RESULTS

Compared with the frequency of 0.04 in nonobese healthy subjects, the S363 allele was significantly higher in obesity clinic patients (0.17; p = 5.6 x 10(-8)), subjects with diabetes who were also obese (0.09; p = 0.0045), subjects with hypertension who were also overweight (0.08; p = 0.0016), and overweight healthy subjects (0.12; p = 0.0004).

DISCUSSION

The NR3C1 N363S variant is associated with obesity and overweight in a range of patient settings but is not associated with hypertension or type 2 diabetes.