Gene-environment interaction and the GNB3 gene in the Atherosclerosis Risk in Communities Study

Objective: The purpose of this study was to investigate the interaction between the G-protein beta-3 (GNB3) 825C>T polymorphism and physical activity in relation to prevalent obesity and hypertension. Research methods and procedures: The GNB3 825C>T genotype was measured in a sample of 14 716 African Americans (AAs) and whites from the Atherosclerosis Risk in Communities (ARIC) study, and logistic regression was used to test for genetic effects and gene-environment interactions. Results: The GNB3 825C>T variant was not independently associated with prevalent obesity or hypertension in either AA or whites. However, we observed a significant interaction (P<0.001) between this variant and physical activity in predicting obesity status in AAs. In AAs who were active, each 825T allele was associated with a 20% lower prevalence of obesity (odds ratio (OR)=0.80, 95% confidence interval (CI)=0.689-0.937, P=0.005), whereas each 825T allele was associated with a 23% greater prevalence of obesity for low-active individuals (OR=1.23, 95% CI=1.06-1.44, P=0.008). We also found a significant interaction between the GNB3 825C>T polymorphism, obesity status and physical activity in predicting hypertension in the AA subjects. AA homozygotes for the 825T allele who were both obese and had a low activity level were 2.7 times more likely to be hypertensive, compared to non-obese, active 825C homozygotes (OR=2.71, 95% CI=1.19-6.17, P<0.02). Discussion: Our findings suggest that the variation within the GNB3 gene may interact with physical activity level to influence obesity status and, together with obesity and physical activity, the GNB3 825C>T variant may influence hypertension prevalence in AAs.