Submitted to: International Journal of Obesity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/6/2006
Publication Date: 6/1/2007
Citation: Grove, M.L., Morrison, A., Folsom, A.R., Boerwinkle, E., Hoelscher, D.M., Bray, M.S. 2007. Gene-environment interaction and the GNB3 gene in the Atherosclerosis risk in communities study. International Journal of Obesity. 31(6):919-926. Interpretive Summary: This study investigated the relationship between obesity and DNA sequence variation in a gene called GNB3, which produces a protein that is important in the regulation of body fat and energy expenditure. Mature African American and white adults were included in this study. In African Americans who were active, each form of the less common DNA sequence variation was associated with a lower risk for obesity, whereas there was a higher risk for obesity for low-active individuals with the same DNA sequence. Variation in the GNB3 gene sequence was also associated with physical activity and hypertension.
Technical Abstract: 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. 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. 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). 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.