The 825T allele of the gene GNB3 which encodes the beta 3 subunit of heterotrimeric G proteins is associated with enhanced signal transduction via G proteins through the generation of a splice variant termed Gbeta3s. It was detected following a classical candidate gene approach using cell lines from patients with enhanced signal transduction and essential hypertension. The high frequency of the 825T allele in 'old' ethnicities, e.g. bushmen and Australian aborigines as well as in black populations, together with its strong association with obesity suggests that the 825T allele is a true 'thrifty genotype'. Development of obesity associated with the 825T allele is strongly influenced by lifestyle, e.g. physical activity, and other exogenous influences like pregnancy. In hypertension the 825T allele is associated with low renin activity and appears to strongly predict the development of left ventricular hypertrophy. In type 2 diabetes the 825T allele was reported to be predispose for end-stage renal disease, whereas this effect has not yet been confirmed for patients with type 1 diabetes.