Alpha- and beta-adrenergic receptor polymorphisms in hypertensive and normotensive offspring

Abstract

Background 

The offspring of hypertensive families are characterized by higher arterial blood pressure values and a depressed autonomic control of heart rate. The present study aimed to verify whether these differences are associated with a different genotype distribution of functionally relevant polymorphisms of the alpha- and beta-adrenergic receptor (AR) genes.

Methods 

We selected 109 age- and sex-matched young normotensive subjects with (FH+, n = 56) and without (FH−, n = 53) a family history of hypertension who underwent evaluation of arterial pressure; 24-h electrocardiogram monitoring to assess time-domain parameters of autonomic heart rate control [i.e. mean RR interval (NN), SD of RR intervals (SDNN) and mean square root of the differences of consecutive RR intervals (rMSSD)]; spectral baroreflex sensitivity measurement; and echo-Doppler to assess diastolic function and left ventricular mass. They were also characterized for the following polymorphisms by means of polymerase chain reaction-restriction fragment polymorphism analysis: Arg492Cys in the α_1a-AR; Del301-303 in the α_2b-AR; Ser49Gly and Arg389Gly in the β₁-AR; and the 5′ leader cistron Arg19Cys, Arg16Gly and Gln27Glu in the β₂-AR.

Results 

FH+ individuals showed a higher systolic pressure, a lower SDNN and a greater isovolumic relaxation time compared to normotensive offspring. No differences were found between the two groups when genotype distribution of the studied polymorphisms was considered. Subjects carrying α_1a-AR Cys492 allelic variant showed lower values of NN, SDNN and rMSSD, independent of age, gender and body mass index.

Conclusions 

The functionally relevant polymorphisms of α_2b-, β₁- and β₂-AR genes are not associated with a family history of essential hypertension. The Arg492Cys polymorphism of the α_1a-AR gene, although not associated with a family history of hypertension, was strongly related to autonomic control of heart rate.