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

Abstract

Objective: The purpose of this study was to investigate the interaction between the G-protein beta-3 (GNB3) 825C4T polymorphism and physical activity in relation to prevalent obesity and hypertension. Research methods and procedures: The GNB3 825C4T 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 825C4T variant was not independently associated with prevalent obesity or hypertension in either AA or whites. However, we observed a significant interaction (Po0.001) 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) ¼ 0.80, 95% confidence interval (CI) ¼ 0.689-0.937, P ¼ 0.005), whereas each 825T allele was associated with a 23% greater prevalence of obesity for low-active individuals (OR ¼ 1.23, 95% CI ¼ 1.06-1.44, P ¼ 0.008). We also found a significant interaction between the GNB3 825C4T 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 ¼ 2.71, 95% CI ¼ 1.19-6.17, Po0.02). 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 825C4T variant may influence hypertension prevalence in AAs.

Influence of fat intake and BMI on the association of rs1799983 NOS3 polymorphism with blood pressure levels in an Iberian population

“…This observation is consistent with the results of Abdel-Aziz et al, who described that the association of obesity with TT genotype of rs1799983 polymorphism increased the risk to develop premature coronary artery disease in Egyptians [11]. Moreover, previous studies have identified the influence of obesity on the relationship between different polymorphisms and BP levels or hypertension among adults and children [35][36][37]. Initial epidemiological studies suggesting a relationship between obesity and BP levels have been supported with the understanding of potential mechanisms involved in both conditions, such as vascular and systemic insulin resistance, dysfuntion of the sympathetic nervous system and the renin-angiotensin-aldosterone system, among other pathogenetic factors [10,38].…”

Perspective on the future use of genomics in exercise prescription

“…So, while there are many obstacles yet to surmount before genomic medicine becomes a reality (8,11,22), we can anticipate that future screening for genomic factors predicted to result in an adverse response of an at-risk phenotype to exercise prescription can improve treatment in susceptible patients. Preliminary findings in the areas of exercise and insulin sensitivity (5,28,29) and exercise and obesity (12,26) suggest that such genomic factors are being identified. While we await additional discoveries, exercise should certainly remain the first line of prescription for the many phenotypes positively impacted by this important treatment; however, we can recognize that this standard of care is not optimal for some patients and envision the future application of genomic information to improve and individualize exercise prescription.…”

Interaction of G-protein 3 Subunit and Nitric Oxide Synthase Gene Polymorphisms on Carotid Artery Intima-media Thickness in Young Adults: The Bogalusa Heart Study

“…14,23,26 The current study demonstrates the interaction effect of GNB3 C825T and eNOS G894T polymorphisms on carotid IMT in young adults. This observation on a community-based cohort is noteworthy in that the participants are free of selection bias of studies involving relatively older adults with clinical CV morbidity.…”

“…An 80-bp product was amplified using 0.9 µmol/l each of the forward primer 5′-TCCCACGAGCATCATCTG-3′ and the reverse primer 5′-TCGTCGTAGCCAGCGAATAGT-3′, 0.2 µmol/leach of the sequence-specific probes 5′-6FAM-CATCACGTCCGTGGCCTTCTCC-TAMRA-3′ and 5′-VIC-CATCACGTCTGTGGCCTT CTCCCT-TAMRA-3′, 1 × TaqMan Universal PCR master mix containing AmpliTaq Gold DNA polymerase and 3 ng DNA in a 5.5 µl reaction volume. 23 Based on the analysis of 67 pairs of blind duplicates, there was 100% concordance in genotyping.…”