Association of hypertension with beta(2)- and alpha(2c10)-adrenergic receptor genotype

The adrenergic receptors have been implicated in the pathogenesis of essential hypertension. We hypothesized that hypertension is associated with variants at the beta(2)-adrenergic receptor locus and at one of the alpha(2)-adrenergic receptor loci. In unrelated individuals, we measured untreated blood pressure and characterized each subject as hypertensive or normotensive. We then used genomic DNA to identify beta(2)- and alpha(2c10)-adrenergic receptor restriction fragment length polymorphisms. In 175 subjects (49% with hypertension, 55% black), both hypertension and race were associated with genotype at the beta(2) locus (chi(2) for hypertension=11, P=.004; chi(2) for race=8.8, P=.012). The association with hypertension persisted in each race group separately (blacks only: chi(2)=9.6, P=.008; whites only: chi(2)=14.2, P=.001). This association persisted in a logistic model that controlled for race (P=.01). Genotype was also significantly associated with baseline systolic, diastolic, and mean arterial blood pressures (p=.05, .01, and .02, respectively). These data suggest that the beta(2)-adrenergic receptor gene is a candidate gene for hypertension in blacks and whites. We also genotyped subjects at the alpha(2)-adrenergic receptor coded on chromosome 10. There was no association between hypertension and genotype at the alpha(2c10) locus in the total group or in blacks, but there was significant association in whites (chi(2)=6.7, P=.03). These data suggest that the beta(2)- and alpha(2c10)-adrenergic receptor genes may contribute, in a race-specific manner, to the inheritance of essential hypertension. Linkage studies in related individuals are needed to confirm these findings.