Association analysis of Arg16Gly polymorphism of the β2-adrenergic receptor gene in offspring from hypertensive and normotensive families

Objective: Since beta(2)-adrenergic receptors (beta(2)AR) can influence blood pressure not only by vasodilation, but also participate in noradrenaline release from sympathetic nerve endings, we have studied whether Arg16Gly polymorphism of the beta(2)AR gene is associated with predisposition to essential hypertension and increased plasma noradrenaline concentration in offspring from normotensive (SN) and hypertensive parents (SH). Design and methods: The study population consisted of 105 young SN and 101 SH subjects matched for age and body mass index. Arg16Gly polymorphism of the beta(2)AR gene was determined by polymerase chain reaction (PCR) technique and subsequent incubation with NcoI restriction enzyme. Resulting fragments were separated using electrophoresis on a 4.2% Metaphor agarose gel. Results: SH already had significantly higher systolic BP, and a tendency to higher diastolic BP than the SN group. The frequency of Arg/Arg homozygotes was significantly increased in SH when compared to SN (25% vs 15%). Results of logistic regression analysis showed the highest relative risk for the Arg/Arg genotype and suggested a recessive action of the Arg16 variant. There was an increased diastolic BP in Arg/Arg homozygotes of the SN group (p = 0.029). This genotype also had a tendency to increased heart rate in both groups (p = 0.049). There was no relationship of this polymorphism with plasma noradrenaline concentration. Conclusion: Our findings suggest that genetic variability of the beta(2)AR gene is implicated in predisposition to essential hypertension. However, the contradictory results between individual studies indicate that the action of the beta(2)AR gene is indirect, through multiple intermediate phenotypes and gene interactions.