Effects of Dopamine Receptor Type 1 and Gs Protein α Subunit Gene Polymorphisms on Blood Pressure at Rest and in Response to Stress

Background: Exaggerated blood pressure (BP) response to behavioral stress has been recognized as an independent predictor of increased BP levels in human subjects. The coupling of dopamine receptor type 1 (DRD1) with stimulatory G-proteins plays an important role in BP regulation. Therefore, we investigated whether the A-48G polymorphism of the DRD1 gene and the T393C polymorphism of the Gs protein α subunit (GNAS) gene influenced BP levels at rest and in response to stress. Methods: A total of 912 white and African American (44.5%) twin subjects (17.4 ± 3.4 years) were genotyped. Systolic and diastolic BP were measured at rest and during two 10-min stress tasks (a social competence interview and a virtual reality car driving simulation test). Regular association analyses and sibpair transmission disequilibrium tests were performed. The two polymorphisms, A-48G (DRD1) and T393C (GNAS), were genotyped by polymerase chain reaction with restriction digestion enzymes. Results: A dominant BP-lowering effect of the -48G allele was observed on diastolic BP at rest (P = .032) and in response to the car driving simulation test (P = .046). The 393C allele was associated with higher systolic BP levels during the social competence interview (P = .024) and the car driving simulation test (P = .016). There were no statistical significances between the two loci for systolic and diastolic BP at rest and during stress. Conclusions: Our findings suggest that DRD1 and GNAS loci contribute to BP regulation at rest, and in particular, in response to behavioral stress. The BP measurement during behavioral stress may have added value for gene association studies.