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 × 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.