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 5363 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.