A functional GNAS promoter polymorphism is associated with altered weight loss during short-term fasting.

In mice, heterozygous knockout of the stimulatory G protein Gas results in obesity which suggests a key role of Gas in body weight regulation. We have recently identified a functional G(-1211)A promoter polymorphism in the human GNAS gene encoding Gas, the GG genotype being associated with increased promoter activity and lipolysis in vitro and increased weight loss capacity in vivo. The present study aimed to independently confirm these results. We genotyped 87 subjects who underwent a 7-day modified fast for the GNAS polymorphism and recorded weight, hunger, and mood. While both mood and hunger were not dependent on genotype, GNAS genotypes were significantly associated with weight loss (GG: -5.0 +/- 1.5 kg, n = 28; AG: -4.2 +/- 1.1 kg, n = 50; AA: -3.2 +/- 1.2, n = 9; p = 0.0003). The present study reconfirms our earlier reported findings and suggests that GNAS genotypes also influence weight loss during short-term fasting. related to a low vascular density (CD31 expression) in CDC.