Association Analysis of Arg16Gly Polymorphism of the β 2 -Adrenergic Receptor Gene in Offspring from Hypertensive and Normotensive Families

Abstract

Objective: Since g 2 -adrenergic receptors ( g 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 g 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 g 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 g 2 AR gene is implicated in predisposition to essential hypertension. However, the contradictory results between individual studies indicate that the action of the g 2 AR gene is indirect, through multiple intermediate phenotypes and gene interactions.