ObjectiveThe 825T allele of the G protein β3 subunit is associated with hypertension in Caucasians. To generate a novel hypothesis regarding the underlying mechanisms, we examined for a potential association of the 825T allele with obesity in hypertension.Patients and methodsWe genotyped 197 hypertensive individuals (104 men, 93 women; mean age 54 years) recruited from the general population in the Heidelberg (Germany) area. Data acquisition included age at first diagnosis of hypertension, body weight and height, actual treated blood pressure values, and history of stroke and/or myocardial infarction (cardiovascular events).ResultsThe 825T allele was significantly (P= 0.02) associated with body mass index (BMI), mean values being 28.6 ± 4.1, 27.0 ± 3.1, and 26.1 ± 3.8 kg/m2for TT, TC, and CC respectively, which persisted after correction for sex and age. The 825T allele frequency was 23.8, 31.4 and 40.0% in individuals with normal weight (BMI < 24.9 kg/m2), overweight (BMI 25.0–29.9 kg/m2), and obesity (BMI >29.9 kg/m2), respectively. Odds ratio for obesity versus normal weight was 3.9 [95% confidence interval (CI) 1.1–14.3;P= 0.03] for TT/CC and 1.8 (95% CI 0.7–4.6;P= 0.18) for TC/CC. BMI and age, but not genotype were significantly correlated with cardiovascular events as determined by logistic regression analysis.ConclusionsThe findings suggest an association between obesity and the 825T allele, a genetic marker for enhanced G protein reactivity, in hypertensive individuals.